Phospho-AMPA Receptor 1 (GluA1) (Ser845) (D10G5) Rabbit mAb #8084

AMPA- (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), kainate-, and NMDA- (N-methyl-D-aspartate) receptors are the three main families of ionotropic glutamate-gated ion channels. AMPA receptors (AMPARs) are comprised of four subunits (GluR 1-4), which assemble as homo- or hetero-tetramers to mediate the majority of fast excitatory transmissions in the central nervous system. AMPARs are implicated in synapse formation, stabilization, and plasticity (1). In contrast to GluR 2-containing AMPARs, AMPARs that lack GluR 2 are permeable to calcium (2). Post-transcriptional modifications (alternative splicing, nuclear RNA editing) and post-translational modifications (glycosylation, phosphorylation) result in a very large number of permutations, fine-tuning the kinetic properties of AMPARs. Research studies have implicated activity changes in AMPARs in a variety of diseases including Alzheimer’s, amyotrophic lateral sclerosis (ALS), stroke, and epilepsy (1).
The activation of PKA regulates the activity of AMPA-type glutamate receptors by phosphorylation of the subunit GluR 1 at Ser845. Furthermore, Ser845 phosphorylation is increased by activation of D1-type dopamine receptors and by inhibition of protein phosphatase 1/protein phosphatase 2A (3,4). Phosphorylation at either Ser831 or Ser845 potentiates AMPA receptor ion channel function: long-term potentiation (LTP) correlates with increased phosphorylation, while long-term depression (LTD) correlates with a dephosphorylation of GluR 1 (5). Phosphomutant mice (Ser831Ala and Ser845Ala) show deficits in LTD and LTP. Either Ser831 or Ser845 alone may support LTP, while only Ser845 is critical for LTD. Furthermore, these mice have memory deficiencies in spatial learning tasks (6,7). Assembly of the β2-adrenergic receptor, trimeric Gs protein, adenyl cyclase, PKA, GluR 1, stargazin, and PSD95 signaling complex for localized cAMP signaling is dependent on phosphorylation of GluR 1 at Ser845 (8).