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.
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: A Soren
authors.initials: AS
authors.lastname: Leonard
authors.forename: Olena
authors.initials: O
authors.lastname: Yermolaieva
authors.forename: Alesia
authors.initials: A
authors.lastname: Hruska-Hageman
authors.forename: Candice C
authors.initials: CC
authors.lastname: Askwith
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Price
authors.forename: John A
authors.initials: JA
authors.lastname: Wemmie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D062565:Acid Sensing Ion Channels; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: C568266:ASIC1 protein, human; C568267:ASIC1 protein, mouse; C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D015222:Sodium Channels; D017868:Cyclic AMP-Dependent Protein Kinases