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, Elena Petroff, Alesia Hruska-Hageman, Candice C. Askwith, Margaret P. Price, John A. Wemmie, Michael J. Welsh

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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.

Original languageEnglish
Pages (from-to)2029-2034
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number4
DOIs
StatePublished - 18 Feb 2003

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Acid Sensing Ion Channels
Cyclic AMP-Dependent Protein Kinases
Carrier Proteins
Phosphotransferases
Phosphorylation
Proteins
PDZ Domains
Neuronal Plasticity
Acidosis
Brain Ischemia

Cite this

Leonard, A. Soren ; Petroff, Elena ; Hruska-Hageman, Alesia ; Askwith, Candice C. ; Price, Margaret P. ; Wemmie, John A. ; Welsh, Michael J. / cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 4. pp. 2029-2034.
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title = "cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1",
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.",
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cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1. / Leonard, A. Soren; Petroff, Elena; Hruska-Hageman, Alesia; Askwith, Candice C.; Price, Margaret P.; Wemmie, John A.; Welsh, Michael J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 4, 18.02.2003, p. 2029-2034.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Leonard, A. Soren

AU - Petroff, Elena

AU - Hruska-Hageman, Alesia

AU - Askwith, Candice C.

AU - Price, Margaret P.

AU - Wemmie, John A.

AU - Welsh, Michael J.

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AB - 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.

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