cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1.

The acid-sensing ion channel-1 (ASIC1) contributes to synaptic plasticity and may influence the response to cerebral ischemia and acidosis. We found that cAMP-dependent protein kinase phosphorylated heterologously expressed ASIC1 and endogenous ASIC1 in brain slices. ASIC1 also showed significant phosphorylation under basal conditions. Previous studies showed that the extreme C-terminal ...
residues of ASIC1 bind the PDZ domain of the protein interacting with C-kinase-1 (PICK1). We found that protein kinase A phosphorylation of Ser-479 in the ASIC1 C terminus interfered with PICK1 binding. In contrast, minimizing phosphorylation or mutating Ser-479 to Ala enhanced PICK1 binding. Phosphorylation-dependent disruption of PICK1 binding reduced the cellular colocalization of ASIC1 and PICK1. Thus, the ASIC1 C terminus contains two sites that influence its binding to PICK1. Regulation of this interaction by phosphorylation provides a mechanism to control the cellular localization of ASIC1.
Mesh Terms:
Amino Acid Sequence, Animals, COS Cells, Carrier Proteins, Cyclic AMP-Dependent Protein Kinases, Hippocampus, Membrane Proteins, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Phosphorylation, Protein Binding, Sodium Channels
Proc. Natl. Acad. Sci. U.S.A.
Date: Feb. 18, 2003
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