The Acid-sensitive, Anesthetic-activated Potassium Leak Channel, KCNK3, Is Regulated by 14-3-3 beta-dependent, Protein Kinase C (PKC)-mediated Endocytic Trafficking

作者：Gabriel Luke; Lvov Anatoli; Orthodoxou Demetra; Rittenhouse Ann R; Kobertz William R; Melikian Haley E^*

来源：Journal of Biological Chemistry, 2012, 287(39): 32354-32366.

DOI：10.1074/jbc.M112.391458

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 down-regulated by PKC; however, the mechanisms responsible for PKC-induced KCNK3 down-regulation are undefined. Here, we report that endocytic trafficking dynamically regulates KCNK3 activity. Phorbol esters and Group I metabotropic glutamate receptor (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 14-3-3 beta and a novel potassium channel endocytic motif, because depleting either 14-3-3 beta 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 14-3-3 beta-dependent regulated trafficking, providing a straightforward mechanism to modulate neuronal excitability and synaptic plasticity by Group I mGluRs.

• 出版日期2012-9-21