cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1
- A. Soren Leonard*,†,
- Olena Yermolaieva*,
- Alesia Hruska-Hageman*,†,
- Candice C. Askwith*,†,
- Margaret P. Price*,
- John A. Wemmie‡, and
- Michael J. Welsh*,†,§,¶
- Departments of *Internal Medicine, ‡Psychiatry, and §Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, †Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242
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Contributed by Michael J. Welsh
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.
Footnotes
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↵ ¶ To whom correspondence should be addressed. E-mail: michael-welsh{at}uiowa.edu.
- Abbreviations:
- ASIC1,
- acid-sensing ion channel-1;
- ASIC1/PEP,
- ASIC1 peptide;
- PKA,
- protein kinase A;
- IBMX,
- 3-isobutyl-1-methylxanthine;
- ASIC/C-term,
- polyhistidine fusion proteins containing the C-terminal region;
- CaMKII,
- calmodulin-dependent protein kinase II
- Copyright © 2003, The National Academy of Sciences
