gria1a (glutamate receptor, ionotropic, AMPA 1a) is one of two zebrafish co-orthologs of vertebrate GRIA1 (GluA1), retained from the teleost-specific genome duplication; its paralog is gria1b. It encodes an AMPA-type ionotropic glutamate receptor subunit, a four-segment membrane protein that assembles into tetrameric glutamate-gated cation channels at excitatory postsynaptic sites and mediates fast excitatory synaptic transmission. The protein keeps the glutamate-binding residues, the channel pore and M2-M3 gating segment, and the C-terminal phosphorylation serines of mammalian GluA1, and it is the more conserved of the two copies. gria1a is expressed by 24 hours post-fertilization in many neuronal populations of the developing brain (including telencephalon, olfactory bulb, habenula, thalamus, hypothalamus, tectum and hindbrain), retina and spinal cord, and is the more abundant copy in larvae. No loss-of-function study of gria1a 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: gria1a 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. 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. gria1a 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: PMID:35221915 Postsynaptic markers for glutamatergic transmission include genes such as grin1a and gria1a, which build NMDA and AMPA receptors, (respectively), present only on the postsynaptic cell membrane. |
| 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. gria1a keeps the C-terminal phosphorylation serines. 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: Do gria1a and gria1b co-assemble in the same AMPA receptors, and in which neurons does each copy dominate (single-cell or double in situ data at larval and adult stages)?
Q: Which copy, or the double mutant, produced the gria1 pallium activity phenotype in the Thyme et al. 2019 schizophrenia-gene screen?
Experiment: Compare gria1a, gria1b and double mutants (with alleles that avoid nonsense-mediated decay, or promoter deletions) for brain activity maps, AMPA mEPSCs in identified neurons and paralog mRNA levels.
Hypothesis: gria1a and gria1b are partly redundant in forebrain excitatory transmission.
Type: genetic interaction
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