SPG11 encodes spatacsin, a large cytoplasmic/peripheral membrane-associated protein that functions with SPG15/spastizin and AP-5 in endolysosomal membrane remodeling. The strongest protein-homeostasis evidence supports a core role in autophagic lysosome reformation, lysosomal tubulation, lysosome membrane recycling, and ER-linked lysosome trafficking/organization. SPG11 also has supported neuronal axonal/synaptic transport contexts, but its principal described cellular role is endolysosomal membrane remodeling.
Definition: A lysosome organization process in which autolysosomal membranes tubulate and give rise to new functional lysosomes after autophagic degradation.
Justification: SPG11/spatacsin and SPG15/spastizin are described as pivotal for ALR and essential for initiation of lysosomal tubulation, but the review currently must use broader lysosome organization and lysosomal membrane organization terms.
Parent term: lysosome organization
Supporting Evidence:
Definition: A lysosome organization process that recycles lysosomal membrane components from autolysosomes or lysosome-derived carriers to regenerate functional lysosomes.
Justification: SPG11/spatacsin is required for lysosome membrane recycling and recruits dynamin for this process, but existing GO terms are broader than the specific recycling step.
Parent term: lysosomal membrane organization
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: SPG11/spatacsin is mainly cytoplasmic and functions as a cytoplasmic/peripheral membrane-associated endolysosomal remodeling factor. Reason: Retain cytoplasm as a core broad location, while relying on ER, late endosome, lysosome, and lysosomal membrane terms for more specific context. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0007409 axonogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Axonogenesis is plausible from orthology and disease biology, but human experimental evidence more directly supports axonal maintenance/transport defects than a core developmental axonogenesis role. Reason: Retain as non-core neuronal/developmental context rather than the proteostasis core function. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0007268 chemical synaptic transmission | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Chemical synaptic transmission is a plausible neuronal consequence of SPG11 dysfunction, but the direct evidence centers on synaptic vesicle/cargo transport defects. Reason: Retain as non-core neuronal phenotype/context. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0008088 axo-dendritic transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Axo-dendritic transport is supported by impaired anterograde vesicle trafficking in SPG11-deficient neurons, but it is secondary to the endolysosomal proteostasis core. Reason: Retain as non-core neuronal transport biology. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0030424 axon | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Axon localization is supported in neurons, but it reflects the neuronal disease/transport context rather than the core ALR function. Reason: Retain as non-core neuronal localization. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cell projection, axon PMID:24794856 spatacsin was located in axons and dendrites |
| GO:0030425 dendrite | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dendrite localization is supported in neurons, but it reflects the neuronal disease/transport context rather than the core ALR function. Reason: Retain as non-core neuronal localization. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cell projection, dendrite PMID:24794856 spatacsin was located in axons and dendrites |
| GO:0045202 synapse | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Synapse localization is supported by neuronal/synaptosome evidence, but it is secondary to the lysosome reformation and membrane-remodeling function. Reason: Retain as non-core neuronal localization. Supporting Evidence: PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0048489 synaptic vesicle transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Synaptic vesicle transport is supported in neuronal models, but it is a secondary neuronal consequence/context for this proteostasis review. Reason: Retain as non-core neuronal transport biology. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nucleus is reported in early localization evidence but UniProt notes that SPG11 is mainly cytoplasmic, and the proteostasis literature centers on endolysosomal remodeling. Reason: Retain as a non-core reported location rather than a defining SPG11 location. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Nucleus file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Cytosol is supported by UniProt/HPA-style localization and is compatible with a large cytoplasmic scaffold associated with endolysosomal membranes. Reason: Retain cytosol as a core broad location, not as a substitute for the more specific endolysosomal/ER locations. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0030424 axon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Axon localization is supported in neurons, but it reflects the neuronal disease/transport context rather than the core ALR function. Reason: Retain as non-core neuronal localization. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cell projection, axon PMID:24794856 spatacsin was located in axons and dendrites |
| GO:0030425 dendrite | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Dendrite localization is supported in neurons, but it reflects the neuronal disease/transport context rather than the core ALR function. Reason: Retain as non-core neuronal localization. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cell projection, dendrite PMID:24794856 spatacsin was located in axons and dendrites |
| GO:0005515 protein binding | IPI PMID:23825025 Interaction between AP-5 and the hereditary spastic parapleg... | MODIFY | Summary: The AP-5/SPG11/SPG15 interaction is real, but generic protein binding obscures the endolysosomal coat/scaffold role. Reason: Replace generic binding with lysosomal membrane organization for the AP5-SPG11-SPG15 coat-like complex context. Proposed replacements: lysosomal membrane organization lysosome organization Supporting Evidence: PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 AP-5, SPG15, and SPG11 form a coat-like complex |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: This proteome-scale interactome evidence is too generic to define an SPG11 molecular function. Reason: Avoid retaining GO:0005515 when no SPG11-specific mechanism is curated from the evidence. Supporting Evidence: file:human/SPG11/SPG11-notes.md Proteome-scale interactome rows from PMID:25416956 and PMID:33961781 are insufficiently informative for core GO curation without a mechanism specific to SPG11 file:human/SPG11/SPG11-notes.md Generic `GO:0005515 protein binding` is overused in this record. |
| GO:0005515 protein binding | IPI PMID:29949766 Inhibition of Lysosome Membrane Recycling Causes Accumulatio... | MODIFY | Summary: The dynamin interaction is mechanistic, but the informative function is lysosome membrane recycling/lysosome organization. Reason: Replace generic protein binding with lysosome organization/lysosomal membrane organization. Proposed replacements: lysosome organization lysosomal membrane organization Supporting Evidence: PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: This proteome-scale interactome evidence is too generic to define an SPG11 molecular function. Reason: Avoid retaining GO:0005515 when no SPG11-specific mechanism is curated from the evidence. Supporting Evidence: file:human/SPG11/SPG11-notes.md Proteome-scale interactome rows from PMID:25416956 and PMID:33961781 are insufficiently informative for core GO curation without a mechanism specific to SPG11 file:human/SPG11/SPG11-notes.md Generic `GO:0005515 protein binding` is overused in this record. |
| GO:0005515 protein binding | IPI PMID:36096339 Cytosolic sequestration of spatacsin by Protein Kinase A and... | MARK AS OVER ANNOTATED | Summary: PKA/14-3-3-dependent interaction regulates spatacsin trafficking, but generic protein binding is not an informative GO function for SPG11. Reason: Do not retain generic protein binding as a core molecular function; capture this as regulatory context in notes/questions instead. Supporting Evidence: PMID:36096339 identified a subset of 14-3-3 proteins as physiological interactors of spatacsin PMID:36096339 The interaction is modulated by Protein Kinase A (PKA)-dependent phosphorylation of spatacsin at Ser1955 file:human/SPG11/SPG11-notes.md Generic `GO:0005515 protein binding` is overused in this record. |
| GO:0005515 protein binding | IPI PMID:37871017 Spatacsin regulates directionality of lysosome trafficking b... | MODIFY | Summary: The AP5Z1/spastizin interaction/regulation evidence is real, but the useful function is ER-linked tubular lysosome formation and lysosome trafficking directionality. Reason: Replace generic binding with lysosome organization, which better captures the functional outcome. Proposed replacements: lysosome organization Supporting Evidence: PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0005515 protein binding | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | MODIFY | Summary: The structural paper defines AP5-SPG11-SPG15 assembly and membrane remodeling, not a useful standalone generic protein-binding function. Reason: Replace generic binding with membrane bending and lysosomal membrane organization. Proposed replacements: membrane bending lysosomal membrane organization Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0042802 identical protein binding | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | MODIFY | Summary: The homomeric/complex assembly evidence is less informative than the demonstrated AP5-SPG11-SPG15 membrane remodeling function. Reason: Replace identical protein binding with membrane bending and lysosomal membrane organization. Proposed replacements: membrane bending lysosomal membrane organization Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: SPG11/spatacsin is mainly cytoplasmic and functions as a cytoplasmic/peripheral membrane-associated endolysosomal remodeling factor. Reason: Retain cytoplasm as a core broad location, while relying on ER, late endosome, lysosome, and lysosomal membrane terms for more specific context. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: Endoplasmic reticulum is supported by recent endogenous localization and functional lysosome-trafficking evidence. Reason: Retain ER as a core functional location for SPG11-dependent tubular lysosome formation and ER-lysosome trafficking regulation. Supporting Evidence: PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synapse localization is supported by neuronal/synaptosome evidence, but it is secondary to the lysosome reformation and membrane-remodeling function. Reason: Retain as non-core neuronal localization. Supporting Evidence: PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: Nucleolus is a weak high-throughput localization relative to the stronger cytoplasmic, ER, late-endolysosomal, and neuronal-process evidence. Reason: Do not treat nucleolus as an informative SPG11 location without stronger gene-specific mechanistic evidence. Supporting Evidence: file:human/SPG11/SPG11-notes.md Nucleolus and plasma membrane HPA rows are weak |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol is supported by UniProt/HPA-style localization and is compatible with a large cytoplasmic scaffold associated with endolysosomal membranes. Reason: Retain cytosol as a core broad location, not as a substitute for the more specific endolysosomal/ER locations. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Plasma membrane is not a defining SPG11 location; PKA/14-3-3 work mentions trafficking from plasma membrane to intracellular space, but core function is endolysosomal/ER membrane remodeling. Reason: Retain only as non-core trafficking/regulatory context. Supporting Evidence: file:human/SPG11/SPG11-notes.md Nucleolus and plasma membrane HPA rows are weak PMID:36096339 identified a subset of 14-3-3 proteins as physiological interactors of spatacsin PMID:36096339 The interaction is modulated by Protein Kinase A (PKA)-dependent phosphorylation of spatacsin at Ser1955 |
| GO:0005634 nucleus | EXP PMID:17322883 Mutations in SPG11, encoding spatacsin, are a major cause of... | KEEP AS NON CORE | Summary: Nucleus is reported in early localization evidence but UniProt notes that SPG11 is mainly cytoplasmic, and the proteostasis literature centers on endolysosomal remodeling. Reason: Retain as a non-core reported location rather than a defining SPG11 location. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Nucleus file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0005764 lysosome | IPI PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome is a supported core compartment for SPG11-dependent ALR, lysosome membrane recycling, and AP5-SPG11-SPG15 membrane remodeling. Reason: Retain as a core endolysosomal location/process context. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0005770 late endosome | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Late endosome is supported by AP5-SPG11-SPG15 membrane sorting/remodeling evidence and AP-5/SPG11/SPG15 colocalization. Reason: Retain as a core endolysosomal compartment for the AP5-SPG11-SPG15 complex. Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 AP-5, SPG15, and SPG11 form a coat-like complex |
| GO:0097212 lysosomal membrane organization | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Lysosomal membrane organization directly captures SPG11-dependent AP5-SPG11-SPG15 membrane remodeling and ALR/tubulation. Reason: Retain as a core process annotation for SPG11 in the proteostasis network. Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation |
| GO:0097753 membrane bending | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Membrane bending is directly supported by the AP5-SPG11-SPG15 structural/mechanistic study, though the lysosomal context should be retained in curation notes. Reason: Retain as a core membrane-remodeling process coupled to lysosomal membrane organization. Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0005764 lysosome | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Lysosome is a supported core compartment for SPG11-dependent ALR, lysosome membrane recycling, and AP5-SPG11-SPG15 membrane remodeling. Reason: Retain as a core endolysosomal location/process context. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0005770 late endosome | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Late endosome is supported by AP5-SPG11-SPG15 membrane sorting/remodeling evidence and AP-5/SPG11/SPG15 colocalization. Reason: Retain as a core endolysosomal compartment for the AP5-SPG11-SPG15 complex. Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 AP-5, SPG15, and SPG11 form a coat-like complex |
| GO:0007040 lysosome organization | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Lysosome organization is the best current GO representation of SPG11-dependent ALR, lysosome membrane recycling, and tubular lysosome formation. Reason: Retain as a core SPG11 function in the proteostasis network. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0007040 lysosome organization | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome organization is the best current GO representation of SPG11-dependent ALR, lysosome membrane recycling, and tubular lysosome formation. Reason: Retain as a core SPG11 function in the proteostasis network. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0007040 lysosome organization | IMP PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome organization is the best current GO representation of SPG11-dependent ALR, lysosome membrane recycling, and tubular lysosome formation. Reason: Retain as a core SPG11 function in the proteostasis network. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0019901 protein kinase binding | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | UNDECIDED | Summary: The available cached PMID:25365221 text supports ALR and lysosomal tubulation, but it does not provide enough evidence to verify protein kinase binding for SPG11. Reason: Leave undecided pending access to the underlying MGI/full-text evidence for this specific molecular-function annotation. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation file:human/SPG11/SPG11-notes.md GO:1905037 autophagosome organization is less precise |
| GO:1905037 autophagosome organization | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | MODIFY | Summary: The cited ALR evidence concerns reformation/tubulation of lysosomes after autophagy, not organization of autophagosomes themselves. Reason: Replace with lysosome organization, which better matches depletion of free lysosomes, autolysosome accumulation, and failure of ALR. Proposed replacements: lysosome organization Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation |
| GO:1905037 autophagosome organization | IMP PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | MODIFY | Summary: The cited ALR evidence concerns reformation/tubulation of lysosomes after autophagy, not organization of autophagosomes themselves. Reason: Replace with lysosome organization, which better matches depletion of free lysosomes, autolysosome accumulation, and failure of ALR. Proposed replacements: lysosome organization Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | Summary: Cytosol is supported by UniProt/HPA-style localization and is compatible with a large cytoplasmic scaffold associated with endolysosomal membranes. Reason: Retain cytosol as a core broad location, not as a substitute for the more specific endolysosomal/ER locations. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0045202 synapse | IDA PMID:24794856 Dysfunction of spatacsin leads to axonal pathology in SPG11-... | KEEP AS NON CORE | Summary: Synapse localization is supported by neuronal/synaptosome evidence, but it is secondary to the lysosome reformation and membrane-remodeling function. Reason: Retain as non-core neuronal localization. Supporting Evidence: PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0008088 axo-dendritic transport | IMP PMID:24794856 Dysfunction of spatacsin leads to axonal pathology in SPG11-... | KEEP AS NON CORE | Summary: Axo-dendritic transport is supported by impaired anterograde vesicle trafficking in SPG11-deficient neurons, but it is secondary to the endolysosomal proteostasis core. Reason: Retain as non-core neuronal transport biology. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0007268 chemical synaptic transmission | IMP PMID:24794856 Dysfunction of spatacsin leads to axonal pathology in SPG11-... | KEEP AS NON CORE | Summary: Chemical synaptic transmission is a plausible neuronal consequence of SPG11 dysfunction, but the direct evidence centers on synaptic vesicle/cargo transport defects. Reason: Retain as non-core neuronal phenotype/context. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0048489 synaptic vesicle transport | IMP PMID:24794856 Dysfunction of spatacsin leads to axonal pathology in SPG11-... | KEEP AS NON CORE | Summary: Synaptic vesicle transport is supported in neuronal models, but it is a secondary neuronal consequence/context for this proteostasis review. Reason: Retain as non-core neuronal transport biology. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | ACCEPT | Summary: Lysosomal membrane association is supported by proteomic evidence and is consistent with SPG11-dependent lysosomal membrane remodeling/recycling. Reason: Retain as a core endolysosomal membrane location, while noting that recent work also supports ER-associated pools. Supporting Evidence: PMID:17897319 identified 58 proteins, known to reside at least partially in the lysosomal membrane PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0005737 cytoplasm | IDA PMID:21545838 Cellular distribution and subcellular localization of spatac... | ACCEPT | Summary: SPG11/spatacsin is mainly cytoplasmic and functions as a cytoplasmic/peripheral membrane-associated endolysosomal remodeling factor. Reason: Retain cytoplasm as a core broad location, while relying on ER, late endosome, lysosome, and lysosomal membrane terms for more specific context. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0031410 cytoplasmic vesicle | IDA PMID:21545838 Cellular distribution and subcellular localization of spatac... | KEEP AS NON CORE | Summary: Cytoplasmic vesicle localization is supported by early antibody localization, but the informative locations are ER, late endosome, lysosome, and lysosomal membrane. Reason: Retain as non-core/broad vesicular context rather than a defining location. Supporting Evidence: PMID:21545838 diffuse punctate, cytoplasmic PMID:21545838 protein-trafficking vesicles, endoplasmic reticulum and microtubules |
| GO:0005515 protein binding | IPI PMID:20613862 A genome-scale DNA repair RNAi screen identifies SPG48 as a ... | MARK AS OVER ANNOTATED | Summary: The interaction evidence supports AP5/SPG15/SPG11 network membership, but generic protein binding is not an informative retained function. Reason: Use the later endolysosomal membrane-remodeling terms for the functional complex; do not retain generic binding as a function. Supporting Evidence: PMID:20613862 putative helicase that interacts with SPG11 and SPG15 file:human/SPG11/SPG11-uniprot.txt Interacts with AP5Z1, AP5B1, AP5S1 and ZFYVE26 file:human/SPG11/SPG11-notes.md Generic `GO:0005515 protein binding` is overused in this record. |
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Download this section (compressed HTML)Q: Should GO add an autophagic lysosome reformation term under lysosome organization so SPG11, SPG15, KIF5B, PIP5K1B, and related ALR factors can be annotated without overusing broad lysosome organization?
Suggested experts: Li Yu, Craig Blackstone, GO biological process editors
Q: Should SPG11 be annotated to a complex/scaffold molecular function, or should AP5-SPG11-SPG15 activity be represented only through biological process terms such as lysosomal membrane organization and membrane bending?
Suggested experts: Margaret Robinson, Yong Ma, GO molecular function editors
Q: What is the best GO representation for SPG11-dependent AP5Z1 degradation and control of lysosome trafficking directionality in neurons?
Suggested experts: Frederic Darios, Giovanni Stevanin, GO biological process editors
Experiment: Rescue SPG11-null cells with SPG11 mutants defective in AP-5/SPG15 binding and quantify ALR after starvation-refeeding, including autolysosome tubulation, free lysosome regeneration, and lysosome membrane recycling.
Hypothesis: AP5-SPG11-SPG15 complex assembly is required for SPG11-dependent autophagic lysosome reformation and lysosomal membrane organization.
Type: genetic rescue/live-cell lysosome imaging
Experiment: Measure membrane curvature sensing and remodeling by purified AP5-SPG11-SPG15 complexes with SPG11 interface mutants on PI3P-containing liposomes.
Hypothesis: SPG11 contributes directly to PI3P-dependent membrane remodeling as part of the AP5-SPG11-SPG15 complex.
Type: in vitro membrane remodeling/structural biochemistry
Experiment: Track lysosome movement in polarized neurons after perturbing SPG11, AP5Z1 degradation, KIF13A, and dynein/dynactin interactions while separately scoring axonal synaptic vesicle transport.
Hypothesis: SPG11-dependent ER/lysosome membrane remodeling controls lysosome trafficking directionality independently from broader synaptic vesicle transport phenotypes.
Type: neuronal live imaging/rescue epistasis
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