Cell Signaling Technology

Product Pathways - Neuroscience

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

Applications Reactivity Sensitivity MW (kDa) Isotype
W IP H M R Endogenous 100 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human  M=Mouse  R=Rat
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

Phospho-AMPA Receptor (GluR 1) (Ser845) (D10G5) Rabbit mAb recognizes endogenous levels of AMPA Receptor (GluR 1) protein only when phosphorylated at Ser845. While the literature refers to this residue as Ser845, it is Ser863 in the UniProt sequence P42261.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser845 of human AMPA Receptor (GluR 1) protein.

Western Blotting

Western Blotting

Western blot analysis of extracts from mouse brain and rat brain using Phospho-AMPA Receptor (GluR 1) (Ser845) (D10G5) Rabbit mAb. The phospho-specificity of the antibody was verified by blocking with a phospho or nonphosphopeptide.

Background

AMPA- (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), kainite-, 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 CNS. AMPARs are implicated in synapse formation, stabilization, and plasticity (1). AMPARs that lack GluR 2 are permeable to calcium, in contrast to GluR 2-containing AMPARs (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).

  1. Palmer, C.L. et al. (2005) Pharmacol Rev 57, 253-77.
  2. Cull-Candy, S. et al. (2006) Curr Opin Neurobiol 16, 288-97.
  3. Roche, K.W. et al. (1996) Neuron 16, 1179-88.
  4. Snyder, G.L. et al. (2000) J Neurosci 20, 4480-8.
  5. Lee, H.K. et al. (2000) Nature 405, 955-9.
  6. Lee, H.K. et al. (2003) Cell 112, 631-43.
  7. He, K. et al. (2009) Proc Natl Acad Sci USA 106, 20033-8.
  8. Joiner, M.L. et al. (2010) EMBO J 29, 482-95.

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For Research Use Only. Not For Use In Diagnostic Procedures.

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