Camp-Dependent Protein Kinase Phosphorylation of the Acid-Sensing Ion Channel-1 Regulates Its Binding to the Protein Interacting with C-Kinase-1

Document Type

Article

Publication Date

2-18-2003

Journal / Book Title

Proceedings of the National Academy of Sciences of the United States of America

Abstract

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.

DOI

10.1073/pnas.252782799

Published Citation

Leonard, A. S., Yermolaieva, O., Hruska-Hageman, A., Askwith, C. C., Price, M. P., Wemmie, J. A., & Welsh, M. J. (2003). cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1. Proceedings of the National Academy of Sciences of the United States of America, 100(4), 2029–2034. https://doi.org/10.1073/pnas.252782799

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