gria1b (glutamate receptor, ionotropic, AMPA 1b) is one of two zebrafish co-orthologs of vertebrate GRIA1 (GluA1), retained from the teleost-specific genome duplication; its paralog is gria1a. It encodes an AMPA-type ionotropic glutamate receptor subunit that, by homology, forms tetrameric glutamate-gated cation channels at excitatory postsynaptic sites. The ligand-binding residues, channel pore and M2-M3 gating segment are identical to those of gria1a and human GRIA1, but gria1b has evolved faster than gria1a since the duplication, most visibly in its cytoplasmic tail, where it lacks serines matching the mammalian CaMKII/PKC (S831) and PKA (S845) phosphorylation sites. gria1b is expressed in many of the same neuronal populations as gria1a in the developing brain, retina and spinal cord, at lower levels in larvae, with an additional otic vesicle domain and RNA-seq signal in ovary, spleen and gill. No loss-of-function study of gria1b alone has been reported.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004971 AMPA glutamate receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: AMPA glutamate receptor activity propagated from the AMPA-receptor node PTN000438081 (donors include human GRIA1 and rodent Gria1-4). Reason: gria1b is a GRIA1 co-ortholog inside the AMPA-receptor clade and keeps every glutamate-binding residue annotated on human GRIA1, the pore loop and the M2-M3 segment. No zebrafish electrophysiology separates the copies, but there is no sign of loss of the receptor function. gria1b has diverged faster than gria1a and its C-terminal tail has lost the serines that correspond to the mammalian CaMKII/PKC and PKA phosphorylation sites, but the ligand-binding and pore residues are intact, so the channel activity itself is not in doubt. Supporting Evidence: PMID:2166337 Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX). file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane propagated from the ionotropic glutamate receptor family node PTN000437926. Reason: AMPA receptor subunits are multi-pass plasma-membrane proteins; the transmembrane and pore segments are fully conserved. Supporting Evidence: file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
| GO:0015276 ligand-gated monoatomic ion channel activity | IEA GO_REF:0000002 | ACCEPT | Summary: Ligand-gated monoatomic ion channel activity from InterPro ionotropic glutamate receptor signatures. Reason: Correct, less specific parent of AMPA glutamate receptor activity. Supporting Evidence: PMID:2166337 Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX). |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Membrane from combined automated annotation (ARBA and InterPro). Reason: Correct but uninformative; the more specific postsynaptic density membrane and plasma membrane terms are also present. Supporting Evidence: file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
| GO:0022824 transmitter-gated monoatomic ion channel activity | IEA GO_REF:0000117 | ACCEPT | Summary: Transmitter-gated monoatomic ion channel activity from an ARBA rule. Reason: Correct parent of AMPA glutamate receptor activity. Supporting Evidence: PMID:2166337 Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX). |
| GO:0032281 AMPA glutamate receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: AMPA glutamate receptor complex propagated from PTN000438081, seeded by rodent Gria1-4 and human GRIA1. Reason: GluA subunits function only as tetrameric AMPA receptor complexes, and the zebrafish subunits keep the features that make up the channel. Zebrafish has eight gria genes that can in principle combine. Supporting Evidence: PMID:18224707 Whereas mammals have four subunit genes, Gria1-4, zebrafish has retained a duplicated set of eight genes named gria1-4a and b. file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000120 | ACCEPT | Summary: Monoatomic ion transmembrane transport inferred from the channel activity terms. Reason: The receptor is a cation channel, so ion flux across the membrane is what it mediates. General but correct. Supporting Evidence: PMID:2166337 Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX). |
| GO:0035235 ionotropic glutamate receptor signaling pathway | IEA GO_REF:0000108 | ACCEPT | Summary: Ionotropic glutamate receptor signaling pathway inferred from AMPA glutamate receptor activity. Reason: Follows directly from the receptor activity. Supporting Evidence: PMID:2166337 Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX). |
| GO:0035249 synaptic transmission, glutamatergic | IBA GO_REF:0000033 | ACCEPT | Summary: Synaptic transmission, glutamatergic propagated from node PTN001826301. Reason: AMPA receptors carry most fast excitatory transmission, and the protein features needed for it are conserved. gria1b is expressed in many neuronal populations of the developing brain, retina and spinal cord. Supporting Evidence: PMID:18224707 As a general rule, each pair of duplicated gria genes is differentially expressed, indicating subfunctionalization of AMPA receptor subunit expression in the teleost lineage. file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
| GO:0043197 dendritic spine | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dendritic spine propagated from PTN000438081, seeded by rodent and human GluA1/GluA2. Reason: The location comes from mammalian synapses. Nothing is known about where either zebrafish GluA1 subunit sits at the subcellular level, and many fish neurons form synapses on dendritic shafts. Kept as plausible but non-core; the postsynaptic density membrane term captures the core location. Supporting Evidence: file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Postsynaptic membrane from the UniProt subcellular location (ARBA). Reason: AMPA receptors are postsynaptic; consistent with the PSD membrane IBA row. Supporting Evidence: file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
| GO:0050804 modulation of chemical synaptic transmission | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Modulation of chemical synaptic transmission propagated from PTN001826301. Reason: In mammals GluA1 is needed for hippocampal LTP, which is regulated partly through phosphorylation of its C-terminal tail. No plasticity experiment exists for either zebrafish copy. gria1b lacks the serines at the positions of the two mammalian regulatory phosphorylation sites, so this role is less secure for gria1b than for gria1a. Supporting Evidence: PMID:10364547 In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. PMID:20716669 Ser831 is a substrate for both CaMKII- and PKC-dependent phosphorylation, whereas Ser845 is a substrate for PKA phosphorylation |
| GO:0060078 regulation of postsynaptic membrane potential | IEA GO_REF:0000108 | ACCEPT | Summary: Regulation of postsynaptic membrane potential inferred from GO:1904315. Reason: Follows from the channel activity at postsynaptic sites. Supporting Evidence: PMID:2166337 Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX). |
| GO:0098839 postsynaptic density membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Postsynaptic density membrane propagated from PTN001826301. Reason: The standard location of AMPA receptors at excitatory synapses; the protein features are conserved. Supporting Evidence: file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
| GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | IBA GO_REF:0000033 | ACCEPT | Summary: Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential, propagated from PTN001826301. Reason: The core activity of an AMPA receptor subunit at the synapse; ligand-binding and pore residues are conserved. Supporting Evidence: PMID:2166337 Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX). file:DANRE/gria1a/gria1a-bioinformatics/RESULTS.md Both copies keep the six glutamate-binding residues, the pore loop and M2-M3 segment, and both palmitoylation cysteines of human GRIA1. |
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Download this section (compressed HTML)Q: Is the gria1b cytoplasmic tail still phosphorylated by CaMKII/PKC or PKA at nearby residues, and does its divergence change synaptic delivery or plasticity of receptors containing it?
Q: Is gria1b expressed in the inner ear and in non-neural tissues (ovary, spleen, gill) as protein, and does gar GRIA1 share these domains?
Experiment: Express gria1a and gria1b (alone and with gria2) in HEK cells or zebrafish neurons; test phosphorylation with phospho-specific assays and measure single-channel conductance and open probability with and without active CaMKII or PKA.
Hypothesis: The diverged gria1b tail makes gria1b-containing receptors insensitive to the CaMKII/PKA regulation that acts on gria1a.
Type: electrophysiology
Experiment: Paralog-specific HCR in situ of gria1a and gria1b in the otic vesicle and inner ear at 24-72 hpf and in adult tissues, with gar GRIA1 as outgroup.
Hypothesis: gria1b has an otic vesicle expression domain absent from gria1a.
Type: expression analysis
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