Ser845

Ser845 refers to a specific serine residue at position 845 in the AMPA receptor subunit GluA1 (GRIA1) in humans. This residue is located in the cytoplasmic C-terminal tail of the GluA1 protein and serves as a phosphorylation site for protein kinase A (PKA) within the cAMP signaling pathway.

Phosphorylation of Ser845 by PKA modulates AMPA receptor trafficking and synaptic strength. In response to increased PKA activity, Ser845 phosphorylation promotes the forward trafficking and synaptic insertion of GluA1-containing receptors, leading to higher surface expression at excitatory synapses and contributing to the maintenance of long-term potentiation. Dephosphorylation of Ser845 can reverse these effects, helping regulate synaptic plasticity.

The region around Ser845 interacts with PDZ-domain scaffolding proteins such as GRIP1/2 and PICK1, which coordinate the trafficking of GluA1 to and from the synapse. The phosphorylation state of Ser845 can influence these protein–protein interactions and thus receptor localization.

Regulation of Ser845 phosphorylation is tied to signaling pathways that activate PKA, such as those triggered by Gs-coupled receptors that elevate cyclic AMP. Phosphatases, including PP1 and calcineurin, counterbalance this modification by dephosphorylating Ser845.

Ser845 is a widely studied site in neuroscience as a molecular marker of PKA activity at glutamatergic synapses. Alterations in Ser845 phosphorylation have been associated with changes in synaptic plasticity, learning, and memory, and may have relevance to neuropsychiatric conditions.