GSBS Student Publications
Title
The Acid-Sensitive, Anesthetic-Activated Potassium Leak Channel, KCNK3, Is Regulated By 14-3-3beta-Dependent, PKC-Mediated Endocytic Trafficking
GSBS Program
Neuroscience
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology; Department of Microbiology and Physiological Systems; Department of Psychiatry
Date
7-30-2012
Document Type
Article
Medical Subject Headings
Nerve Tissue Proteins; Potassium Channels, Tandem Pore Domain; Protein Kinase C; Receptors, Metabotropic Glutamate
Disciplines
Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology
Abstract
The acid-sensitive neuronal potassium leak channel, KCNK3, is vital for setting the resting membrane potential and is the primary target for volatile anesthetics. Recent reports demonstrate that KCNK3 activity is downregulated by PKC; however, the mechanisms responsible for PKC-induced KCNK3 downregulation are undefined. Here, we report that endocytic trafficking dynamically regulates KCNK3 activity. Phorbol esters and Group I mGluR activation acutely decreased both native and recombinant KCNK3 currents with concomitant KCNK3 surface losses in cerebellar granule neurons and cell lines. PKC-mediated KCNK3 internalization required the presence of both 14-3-3beta and a novel potassium channel endocytic motif, as depleting either 14-3-3beta protein levels or ablating the endocytic motif completely abrogated PKC-regulated KCNK3 trafficking. These results demonstrate that neuronal potassium leak channels are not static membrane residents, but are subject to 14-3-3beta-dependent regulated trafficking, providing a straightforward mechanism to modulate neuronal excitability and synaptic plasticity by Group I mGluRs.
Related Resources
Journal Title
The Journal of biological chemistry
PubMed ID
22846993
Repository Citation
Gabriel, Luke; Lvov, Anatoli; Orthodoxou, Demetra; Rittenhouse, Ann R.; Kobertz, William R.; and Melikian, Haley E., "The Acid-Sensitive, Anesthetic-Activated Potassium Leak Channel, KCNK3, Is Regulated By 14-3-3beta-Dependent, PKC-Mediated Endocytic Trafficking" (2012). GSBS Student Publications. 1787.
https://escholarship.umassmed.edu/gsbs_sp/1787
Comments
Citation: J Biol Chem. 2012 Jul 30. DOI 10.1074/jbc.M112.391458. Link to article on publisher's site