Rab35 GTPase Positively Regulates Endocytic Recycling of Cardiac K Channels

Overview

Journal Channels (Austin)

Specialty Biochemistry

Date 2022 Jun 27

PMID 35754325

Authors

Bo Yang

Jia-Lu Yao

Jian-Yi Huo

Yu-Long Feng

William A Coetzee

Guang-Yin Xu

Hua-Qian Yang

Affiliations

Soon will be listed here.

Abstract

ATP-sensitive K (K) channel couples membrane excitability to intracellular energy metabolism. Maintaining K channel surface expression is key to normal insulin secretion, blood pressure and cardioprotection. However, the molecular mechanisms regulating K channel internalization and endocytic recycling, which directly affect the surface expression of K channels, are poorly understood. Here we used the cardiac K channel subtype, Kir6.2/SUR2A, and characterized Rab35 GTPase as a key regulator of K channel endocytic recycling. Electrophysiological recordings and surface biotinylation assays showed decreased K channel surface density with co-expression of a dominant negative Rab35 mutant (Rab35-DN), but not other recycling-related Rab GTPases, including Rab4, Rab11a and Rab11b. Immunofluorescence images revealed strong colocalization of Rab35-DN with recycling Kir6.2. Rab35-DN minimized the recycling rate of K channels. Rab35 also regulated K channel current amplitude in isolated adult cardiomyocytes by affecting its surface expression but not channel properties, which validated its physiologic relevance and the potential of pharmacologic target for treating the diseases with K channel trafficking defects.

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