Gria1 (rat, UniProt P19490) - manual literature synthesis

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written by the reviewer from the cached publications in publications/ and the
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Identity

Gria1 encodes GluA1 (GluR1, GluR-A, GluR-K1), a 907-residue pore-forming subunit of
AMPA-type ionotropic glutamate receptors (RGD:621531, GeneID 50592). Flip and flop
splice isoforms differ in a short extracellular segment that tunes desensitization
[PMID:1699275 "These modules, designated \"flip\" and \"flop,\" are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate."].

Channel activity

• Cloned from rat brain by functional expression as a kainate-gated channel
  PMID:2480522,
  then recognised as AMPA-selective
  PMID:2166337.
• GluA1 carries a genomically encoded Gln at the Q/R site and is not edited; GluA1
  homomers and GluA1/GluA3 receptors are Ca2+-permeable, while co-assembly with
  edited GluA2 abolishes Ca2+ permeability
  PMID:1709304
  PMID:1709304.
  Quantitative Ca2+ permeability of GluR-A(Q) channels was measured by Jatzke et al.
  PMID:11773314.
• Auxiliary subunits: TARPs and cornichons co-assemble with GluA1-containing
  receptors and modulate gating and surface expression
  PMID:19265014
  PMID:17409242.
• Structure: the principal hippocampal AMPAR is a GluA1/GluA2 heteromer with TARP
  gamma-8 PMID:30872532.
  N-terminal domains drive assembly
  PMID:21317873
  PMID:19461580.

Trafficking and plasticity

• GluA1 carries a C-terminal type I PDZ ligand that binds SAP97
  PMID:16634638.
• LTP and CaMKII drive GluA1-containing receptors into synapses by a PDZ-dependent
  mechanism PMID:10731148;
  GluA1/GluA2 receptors are added during plasticity, whereas GluA2/GluA3 receptors
  cycle constitutively PMID:11348590.
• PKA phosphorylation (Ser845 in the mature-protein numbering used by most papers;
  Ser-863 in the UniProt precursor numbering of P19490) controls
  synaptic incorporation PMID:12536214.
  A beta2-adrenergic receptor/Gs/adenylyl cyclase/PKA complex is assembled with GluA1
  through stargazin and PSD-95 PMID:19942860.
• Loop1 CaMKII site S567 regulates synaptic targeting
  PMID:21135237.
• Endocytosis: AMPA- and insulin-induced internalization depend on GluA1 and GluA2
  tail determinants PMID:11100149;
  ubiquitinated GluA1 is internalised via Eps15
  PMID:25023288.
• Transient insertion of GluA2-lacking (GluA1-containing, Ca2+-permeable) receptors
  after LTP-inducing stimuli PMID:22915106.
• Oxygen/glucose deprivation removes GluA2 but leaves surface GluA1 unchanged
  PMID:19321442.
• Palmitoylation by zDHHC3 restrains activity-dependent GluA1 surface delivery
  PMID:29222408.

Localization

Somatodendritic; concentrated at the postsynaptic density membrane of dendritic
spines of glutamatergic synapses, with endosomal, ER and smaller presynaptic pools
PMID:15610164
PMID:16903873.
UniProt notes GluA1 is excluded from axons (by similarity to mouse).

Behaviour and drug-response literature

Many rat annotations come from expression studies in drug, stress, diet or toxin
paradigms (cocaine, morphine, ethanol, lithium, tributyltin, sucrose, leptin, BDNF,
glucocorticoid/miR-132, IL-10 under hypoxia). These report changes in GluA1 protein,
phosphorylation or surface level as a readout; they do not show that GluA1 executes
the "response" process. Knockdown/overexpression studies (CeA GluA1 in morphine CPP,
VTA GluA1 in cocaine motivation, hippocampal GluA1 ASO in inhibitory-avoidance memory)
show necessity of GluA1-containing AMPARs for drug- and memory-related plasticity
PMID:23345231
PMID:19547753.