Arl1 (Arf-like 1; also arflike/Arf72A) is an essential, N-myristoylated Arf-family small GTPase that binds and hydrolyses GTP and associates with the cytoplasmic face of trans-Golgi/TGN membranes. In its GTP-bound form it recruits peripheral proteins to the trans-Golgi: the four GRIP-domain golgins (dGolgin-245, dGolgin-97 and dGCC88 depend on it for Golgi targeting; dGCC185 only weakly), the Arf1 exchange factor Sec71 (BIG1/BIG2 ortholog), and the BAR-domain protein Arfaptin. By recruiting Sec71 it promotes Arf1 activation and AP-1 clathrin adaptor recruitment at the TGN, which larval salivary glands require to form secretory granules. Arl1 is not required for overall Golgi integrity. Loss of Arl1 in photoreceptors expands the Golgi, accelerates secretion and suppresses retinal degeneration caused by a misfolded rhodopsin, and in motor neurons Arl1 acts with Garz and Arfaptin at the Golgi to support synapse growth.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IDA PMID:21693198 Drosophila arf72A acts as an essential regulator of endoplas... | ACCEPT | Summary: Arl1 (Arf72A) localizes to Golgi membranes in fly photoreceptors. Reason: Direct localization of Arl1 to Golgi membranes in vivo; consistent with trans-Golgi localization in S2 cells (PMID:22291037) and Golgi localization in motor neuron soma (PMID:26116655). Golgi membrane is where Arl1-GTP recruits its effectors. Supporting Evidence: PMID:21693198 ARF72A localizes to the Golgi membranes of Drosophila photoreceptor cells, consistent with mammalian Arl1 localization in cell culture systems. PMID:22291037 Thus, Sec71 binds to Arl1-coated liposomes in vitro and colocalizes with Arl1 on the trans-Golgi in vivo. |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Arl1 is an Arf-family small GTPase; recombinant fly protein hydrolyses GTP. Reason: GTP hydrolysis by purified recombinant fly arl protein is reported directly (PMID:1901655, abstract), and Arf-family membership supports it. The GTPase cycle is the switch that controls effector binding. Supporting Evidence: PMID:1901655 including the ability to bind and hydrolyze GTP file:DROME/Arl1/Arl1-uniprot.txt Belongs to the small GTPase superfamily. Arf family. |
| GO:0003924 GTPase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Arl1 is an Arf-family small GTPase; recombinant fly protein hydrolyses GTP. Reason: GTP hydrolysis by purified recombinant fly arl protein is reported directly (PMID:1901655, abstract), and Arf-family membership supports it. The GTPase cycle is the switch that controls effector binding. Supporting Evidence: PMID:1901655 including the ability to bind and hydrolyze GTP file:DROME/Arl1/Arl1-uniprot.txt Belongs to the small GTPase superfamily. Arf family. |
| GO:0005515 protein binding | IPI PMID:22291037 The small G protein Arl1 directs the trans-Golgi-specific ta... | REMOVE | Summary: Bare protein binding with Sec71 (BIG1/BIG2 ortholog). Reason: The Arl1-Sec71 interaction is real and direct (PMID:22291037), but generic protein binding carries no functional information. Its biological meaning, GTP-dependent recruitment of Sec71 to the trans-Golgi, is captured by the protein localization to Golgi membrane rows from the same paper and by the core function. Removal does not dispute the interaction. Supporting Evidence: PMID:22291037 Applying this to Drosophila melanogaster cell extracts revealed a direct interaction between Arl1 and Sec71, the Drosophila ortholog of the trans-Golgi GEFs BIG1/2. |
| GO:0005525 GTP binding | IBA GO_REF:0000033 | ACCEPT | Summary: Arl1 binds GTP. Reason: Purified recombinant fly arl protein binds GTP (PMID:1901655), and the Arf-family GTP-binding motifs are conserved. GTP-bound Arl1 is the effector-binding form (PMID:19001129, PMID:22291037). Supporting Evidence: PMID:1901655 including the ability to bind and hydrolyze GTP PMID:19001129 We initially confirmed that Arl1 was able to bind to dGolgin-245, dGolgin-97, and dGCC88 in a GTP-dependent manner |
| GO:0005525 GTP binding | IDA PMID:1901655 The arflike gene encodes an essential GTP-binding protein in... | ACCEPT | Summary: Arl1 binds GTP. Reason: Purified recombinant fly arl protein binds GTP (PMID:1901655), and the Arf-family GTP-binding motifs are conserved. GTP-bound Arl1 is the effector-binding form (PMID:19001129, PMID:22291037). Supporting Evidence: PMID:1901655 including the ability to bind and hydrolyze GTP PMID:19001129 We initially confirmed that Arl1 was able to bind to dGolgin-245, dGolgin-97, and dGCC88 in a GTP-dependent manner |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: Arl1 binds GTP. Reason: Purified recombinant fly arl protein binds GTP (PMID:1901655), and the Arf-family GTP-binding motifs are conserved. GTP-bound Arl1 is the effector-binding form (PMID:19001129, PMID:22291037). Supporting Evidence: PMID:1901655 including the ability to bind and hydrolyze GTP PMID:19001129 We initially confirmed that Arl1 was able to bind to dGolgin-245, dGolgin-97, and dGCC88 in a GTP-dependent manner |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: Cytoplasm; true but uninformative for a Golgi-associated small GTPase. Reason: Arl1 is a peripheral membrane protein of the cytoplasmic face of the Golgi; cytoplasm is correct but much less specific than the experimentally supported Golgi membrane and trans-Golgi network locations this gene already carries (PMID:21693198, PMID:22291037). Replace with Golgi membrane. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000917851 Broad Arf/Arl/Sar node; cytoplasm is true for its descendants, so the inheritance is sound, but the term is far less specific than Arl1's Golgi membrane location. Proposed replacements: Golgi membrane Supporting Evidence: PMID:21693198 ARF72A localizes to the Golgi membranes of Drosophila photoreceptor cells, consistent with mammalian Arl1 localization in cell culture systems. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | MODIFY | Summary: Cytoplasm; true but uninformative for a Golgi-associated small GTPase. Reason: Arl1 is a peripheral membrane protein of the cytoplasmic face of the Golgi; cytoplasm is correct but much less specific than the experimentally supported Golgi membrane and trans-Golgi network locations this gene already carries (PMID:21693198, PMID:22291037). Replace with Golgi membrane. Proposed replacements: Golgi membrane Supporting Evidence: PMID:21693198 ARF72A localizes to the Golgi membranes of Drosophila photoreceptor cells, consistent with mammalian Arl1 localization in cell culture systems. |
| GO:0005789 endoplasmic reticulum membrane | IGI PMID:21693198 Drosophila arf72A acts as an essential regulator of endoplas... | KEEP AS NON CORE | Summary: More Arl1 is found on the ER in the ninaE(D1) retinopathy photoreceptor model. Reason: The ER localization is reported under a disease-model condition (misfolded rhodopsin accumulating in the ER), not as the normal site of Arl1 action, which is the Golgi/TGN. Full text not available to see the assay; the experimental row is retained but is peripheral to the core function. Supporting Evidence: PMID:21693198 Interestingly, our study indicated that more ARF72A localized on the endoplasmic reticulum in the ninaE(D1) photoreceptor cell, a Drosophila model of autosomal-dominant retinitis pigmentosa, compared to that in the wild-type. |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Arl1 is a Golgi-resident Arf-family GTPase. Reason: Root organelle term. The IBA is consistent with direct fly evidence for Golgi membrane and trans-Golgi localization (PMID:21693198, PMID:22291037) and with Arl1 orthologs in yeast and mammals; the organelle claim holds. Sub-compartment rows (Golgi membrane, trans-Golgi network) are already present. Supporting Evidence: PMID:21693198 ARF72A localizes to the Golgi membranes of Drosophila photoreceptor cells, consistent with mammalian Arl1 localization in cell culture systems. PMID:22291037 Thus, Sec71 binds to Arl1-coated liposomes in vitro and colocalizes with Arl1 on the trans-Golgi in vivo. |
| GO:0005802 trans-Golgi network | IDA PMID:22291037 The small G protein Arl1 directs the trans-Golgi-specific ta... | ACCEPT | Summary: Arl1 colocalizes with Sec71 on the trans-Golgi in S2 cells. Reason: Direct colocalization with a trans-Golgi marker and Sec71 in S2 cells. The trans-Golgi/TGN is the site where Arl1 recruits golgins, Sec71 and, downstream, AP-1 (PMID:24610947). Supporting Evidence: PMID:22291037 Thus, Sec71 binds to Arl1-coated liposomes in vitro and colocalizes with Arl1 on the trans-Golgi in vivo. PMID:24610947 Taken together, these results are consistent with the model that AP-1 is recruited to the TGN and immature secretory granules by Sec71-dependent activation of Arf1 downstream of Arl1. |
| GO:0006886 intracellular protein transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference that Arl1 functions in intracellular protein transport. Reason: Arl1 orthologs act in endosome-to-Golgi and TGN trafficking, and in the fly Arl1 is needed for AP-1 recruitment at the TGN (PMID:24610947), so the process is plausible. The fly's best-supported role is recruitment of peripheral proteins (golgins, Sec71, Arfaptin) to the TGN membrane, not transport of protein cargo itself; this broad transport term is retained as non-core. Supporting Evidence: PMID:24610947 Taken together, these results are consistent with the model that AP-1 is recruited to the TGN and immature secretory granules by Sec71-dependent activation of Arf1 downstream of Arl1. file:DROME/Arl1/Arl1-uniprot.txt GTP-binding protein involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus. |
| GO:0007269 neurotransmitter secretion | TAS PMID:10798391 A genome-wide search for synaptic vesicle cycle proteins in ... | MARK AS OVER ANNOTATED | Summary: Neurotransmitter secretion, from a genome-wide homology survey. Reason: PMID:10798391 lists fly homologs of mammalian genes implicated directly or indirectly in the synaptic vesicle cycle; it reports no experiment on Arl1. No study places fly Arl1 at the synapse; its neuronal role (PMID:26116655) is in Arfaptin recruitment at the Golgi of the motor neuron soma. The term over-states the evidence. Supporting Evidence: PMID:10798391 We screened the fly genome sequence for homologs of mammalian genes implicated directly or indirectly in exocytosis and endocytosis of synaptic vesicles. PMID:26116655 These data demonstrate that both Arl1 and Garz colocalize with Arfip at the GA in motor neurons. file:DROME/Arl1/Arl1-deep-research-manual.md no experiment on Arl1. No study places fly Arl1 at the presynapse or in synaptic vesicle recycling. |
| GO:0016192 vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: Arl1 participates in vesicle-mediated transport at the trans-Golgi. Reason: Arl1 recruits Sec71 and so supports Arf1-dependent AP-1 recruitment at the TGN, required for secretory granule formation (PMID:24610947), and recruits the GRIP-domain golgins that tether incoming carriers. A more specific transport step has not been established in the fly, so this level of description is appropriate. Supporting Evidence: PMID:24610947 Taken together, these results are consistent with the model that AP-1 is recruited to the TGN and immature secretory granules by Sec71-dependent activation of Arf1 downstream of Arl1. PMID:24610947 At a functional level, Arl1 is essential for formation of secretory granules in the larval salivary gland. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000117 | ACCEPT | Summary: Arl1 participates in vesicle-mediated transport at the trans-Golgi. Reason: Arl1 recruits Sec71 and so supports Arf1-dependent AP-1 recruitment at the TGN, required for secretory granule formation (PMID:24610947), and recruits the GRIP-domain golgins that tether incoming carriers. A more specific transport step has not been established in the fly, so this level of description is appropriate. Supporting Evidence: PMID:24610947 Taken together, these results are consistent with the model that AP-1 is recruited to the TGN and immature secretory granules by Sec71-dependent activation of Arf1 downstream of Arl1. PMID:24610947 At a functional level, Arl1 is essential for formation of secretory granules in the larval salivary gland. |
| GO:0019904 protein domain specific binding | IPI PMID:19001129 Golgi coiled-coil proteins contain multiple binding sites fo... | ACCEPT | Summary: Arl1 binds the C-terminal GRIP domain of the four fly GRIP-domain golgins. Reason: Y2H and in vitro pulldowns show GTP-dependent binding of Arl1 to the GRIP domains of dGolgin-245, dGolgin-97, dGCC88 and dGCC185. This domain-specific effector binding underlies Arl1-dependent golgin recruitment (PMID:24610947). Supporting Evidence: PMID:19001129 The mapping data indicate that for all four proteins, the C-terminal GRIP domain binds to Arl1 but not to any of the interacting Rabs PMID:19001129 We initially confirmed that Arl1 was able to bind to dGolgin-245, dGolgin-97, and dGCC88 in a GTP-dependent manner |
| GO:0033363 secretory granule organization | IMP PMID:24610947 The Arf family G protein Arl1 is required for secretory gran... | KEEP AS NON CORE | Summary: Arl1 mutant salivary glands fail to form normal secretory granules. Reason: Well supported by mutant analysis with genomic rescue. The defect appears downstream of Arl1's core activity: Arl1 recruits Sec71 and so promotes Arf1-dependent AP-1 recruitment at the TGN, which the gland needs to make granules. This tissue-specific outcome is retained as non-core. Supporting Evidence: PMID:24610947 At a functional level, Arl1 is essential for formation of secretory granules in the larval salivary gland. PMID:24610947 Taken together, these results are consistent with the model that AP-1 is recruited to the TGN and immature secretory granules by Sec71-dependent activation of Arf1 downstream of Arl1. |
| GO:0034067 protein localization to Golgi apparatus | IMP PMID:24610947 The Arf family G protein Arl1 is required for secretory gran... | MODIFY | Summary: Arl1 is required for Golgi recruitment of three of the four GRIP-domain golgins. Reason: Correct, but the golgins are peripheral proteins recruited to the cytoplasmic face of the Golgi membrane by Arl1-GTP; the more specific child GO:1903292 protein localization to Golgi membrane, which the gene already carries (IDA/IPI, PMID:22291037), fits this evidence. Proposed replacements: protein localization to Golgi membrane Supporting Evidence: PMID:24610947 The gene is essential, and examination of clones of cells lacking Arl1 shows that it is required for recruitment of three of the four GRIP domain golgins to the Golgi, with Drosophila GCC185 being less dependent on Arl1. PMID:24610947 indicating that Arl1 is not required for Golgi integrity but rather has a more specific role in GRIP domain protein recruitment |
| GO:0048488 synaptic vesicle endocytosis | TAS PMID:10798391 A genome-wide search for synaptic vesicle cycle proteins in ... | MARK AS OVER ANNOTATED | Summary: Synaptic vesicle endocytosis, from a genome-wide homology survey. Reason: Same basis as the neurotransmitter secretion row: PMID:10798391 is a homolog listing with no experiment on Arl1, and no evidence places fly Arl1 in synaptic vesicle recycling. Supporting Evidence: PMID:10798391 We screened the fly genome sequence for homologs of mammalian genes implicated directly or indirectly in exocytosis and endocytosis of synaptic vesicles. file:DROME/Arl1/Arl1-deep-research-manual.md no experiment on Arl1. No study places fly Arl1 at the presynapse or in synaptic vesicle recycling. |
| GO:0051649 establishment of localization in cell | IEA GO_REF:0000117 | MODIFY | Summary: ARBA-predicted establishment of localization in cell. Reason: Very general. The more specific intracellular protein transport (IBA) and protein localization to Golgi membrane (IDA) rows describe what is supported. Replace with GO:1903292, the experimentally supported, informative process. Proposed replacements: protein localization to Golgi membrane Supporting Evidence: PMID:24610947 The gene is essential, and examination of clones of cells lacking Arl1 shows that it is required for recruitment of three of the four GRIP domain golgins to the Golgi, with Drosophila GCC185 being less dependent on Arl1. |
| GO:0098793 presynapse | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Presynapse, inferred automatically from the synaptic vesicle endocytosis TAS row. Reason: Derived from the GO:0048488 TAS annotation, itself an over-annotation from a homology survey. No localization data place fly Arl1 at the presynapse; in neurons it colocalizes with Arfaptin at the Golgi of the soma. Supporting Evidence: PMID:26116655 These data demonstrate that both Arl1 and Garz colocalize with Arfip at the GA in motor neurons. |
| GO:1903292 protein localization to Golgi membrane | IDA PMID:22291037 The small G protein Arl1 directs the trans-Golgi-specific ta... | ACCEPT | Summary: Arl1 recruits Sec71 (BIG1/2 ortholog) to the trans-Golgi membrane. Reason: Arl1 directly binds Sec71 and overexpressed Arl1 recruits the Sec71 N-terminal region to the Golgi in S2 cells; in vivo Arl1 is also required for Golgi recruitment of GRIP-domain golgins (PMID:24610947). Recruiting effectors to the Golgi membrane is Arl1's core role. Supporting Evidence: PMID:22291037 However, when it was coexpressed with Drosophila Arl1, this N-terminal region was efficiently recruited to the Golgi PMID:24610947 The gene is essential, and examination of clones of cells lacking Arl1 shows that it is required for recruitment of three of the four GRIP domain golgins to the Golgi, with Drosophila GCC185 being less dependent on Arl1. |
| GO:1903292 protein localization to Golgi membrane | IPI PMID:22291037 The small G protein Arl1 directs the trans-Golgi-specific ta... | ACCEPT | Summary: Arl1 binds Sec71 directly to recruit it to the trans-Golgi. Reason: Same claim as the IDA row; the direct Arl1-Sec71 interaction is the mechanism of recruitment. Supporting Evidence: PMID:22291037 Applying this to Drosophila melanogaster cell extracts revealed a direct interaction between Arl1 and Sec71, the Drosophila ortholog of the trans-Golgi GEFs BIG1/2. PMID:22291037 However, when it was coexpressed with Drosophila Arl1, this N-terminal region was efficiently recruited to the Golgi |
| GO:7770035 negative regulation of ER to Golgi vesicle-mediated transport | IMP PMID:21693198 Drosophila arf72A acts as an essential regulator of endoplas... | KEEP AS NON CORE | Summary: Loss of arf72A expands the Golgi and accelerates protein secretion from the ER. Reason: Experimental phenotype from photoreceptors (abstract only; curator saw the full text). Whether Arl1 regulates ER export directly or the effect follows from altered Golgi/TGN function is not resolved; kept as non-core. Supporting Evidence: PMID:21693198 resulting in over-proliferated Golgi complexes and accelerated protein secretion |
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Download this section (compressed HTML)Q: Which factor activates Arl1 on the Drosophila trans-Golgi: is Garz (GBF1) a direct Arl1 GEF, as the genetic data of PMID:26116655 suggest, or does a SYS1/ARFRP1-type pathway act as in yeast and mammals?
Q: Is the accelerated secretion and ER-to-Golgi shift in arf72A photoreceptors (PMID:21693198) a direct Arl1 role at the ER, or a consequence of lost golgin/Sec71 recruitment at the TGN?
Q: Why is AP-1 recruitment Arl1-dependent in salivary gland but not in all tissues, given that golgin recruitment depends on Arl1 everywhere tested (PMID:24610947)?
Experiment: Measure GEF activity of purified Garz and Sec7-domain proteins on myristoylated Arl1-GDP on liposomes, and test whether Arl1 directly stimulates Sec71 GEF activity toward Arf1.
Experiment: Compare ER exit kinetics (e.g. RUSH reporters) in arl1 null and golgin- or Sec71-depleted photoreceptors or S2 cells to separate direct ER roles from TGN effector-recruitment defects.
ADP ribosylation factor-like 1 (Arl1) encodes an Arf GTPase important for secretory granule maturation and for preventing early degradation of these granules.
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