Recombinant Mouse Glutamate receptor 1 (Gria1), partial

Function

Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:1699805). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate. Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+) (By similarity)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Endoplasmic reticulum membrane (Multi-pass membrane protein); Postsynaptic cell membrane (Multi-pass membrane protein); Postsynaptic density membrane (Multi-pass membrane protein); Cell projection, dendrite; Cell projection, dendritic spine; Early endosome membrane (Multi-pass membrane protein); Recycling endosome membrane (Multi-pass membrane protein); Presynapse; Synapse

Tissue Specificity

Expressed in the outer plexiform layer of the retina of the eye (at protein level) (PubMed:28334377). Expressed in the forebrain and hippocampus (at protein level) (PubMed:31651360)

Subunit

Homotetramer or heterotetramer of pore-forming glutamate receptor subunits (PubMed:1699805, PubMed:33981040). Heteromeric assembly can be the result of both receptor subtype and flip or flop form and according the composition, one partner can be dominant with respect to the fast desensitizing current component, whereas the other can determine the steady-state component (By similarity). Tetramers may be formed by the dimerization of dimers (By similarity). Found in a complex with GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity). Interacts with HIP1 and RASGRF2 (PubMed:12839988, PubMed:16407208). Interacts with SYNDIG1 and GRIA2 (PubMed:20152115). Interacts with DLG1 (via C-terminus). Interacts with LRFN1. Interacts with PRKG2. Interacts with CNIH2 and CACNG2. Interacts with CACNG5; this interaction modulates the gating. Interacts (via C-terminus) with PDLIM4 (via LIM domain); this interaction as well as the interaction of PDLIM4 with alpha-actinin is required for their colocalization in early endosomes. Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (PubMed:23524343). Interacts (via PDZ-binding motif) with SHANK3 (via PDZ domain) (PubMed:16606358). Interacts with CACNG3; associates GRIA1 with the adapter protein complex 4 (AP-4) to target GRIA1 to the somatodendritic compartment of neurons (PubMed:18341993). Interacts with CACNG2; this interaction mediates traffick to the plasma membrane and modulation of desensitization. Interacts with CNIH2 and CNIH3; this interaction promotes expression at the plasma membrane and extensively modulates their gating properties by slowing deactivation and desensitization kinetics (By similarity). Found in a complex with GRIA2, GRIA3, GRIA4, DLG4, CACNG8 and CNIH2 (PubMed:33981040)

• Sakimura K. et al. Functional expression from cloned cDNAs of glutamate receptor species responsive to kainate and quisqualate. — FEBS Lett. (1990)
• Metzler M. et al. Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking. — EMBO J. (2003)
• Hayashi T. et al. Differential regulation of AMPA receptor subunit trafficking by palmitoylation of two distinct sites. — Neuron (2005)
• Tian X. et al. Age-dependent participation of Ras-GRF proteins in coupling calcium-permeable AMPA glutamate receptors to Ras/Erk signaling in cortical neurons. — J. Biol. Chem. (2006)
• Uchino S. et al. Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. — J. Neurochem. (2006)
• Matsuda S. et al. Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4. — Neuron (2008)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)
• Kalashnikova E. et al. SynDIG1: an activity-regulated, AMPA- receptor-interacting transmembrane protein that regulates excitatory synapse development. — Neuron (2010)