Cyclic expression of the voltage‐gated potassium channel KV10.1 promotes disassembly of the primary cilium

Abstract

© 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license. The primary cilium, critical for morphogenic and growth factor signaling, is assembled upon cell cycle exit, but the links between ciliogenesis and cell cycle progression are unclear. K V 10.1 is a voltage-gated potassium channel frequently overexpressed in tumors. We have previously reported that expression of K V 10.1 is temporally restricted to a time period immediately prior to mitosis in healthy cells. Here, we provide microscopical and biochemical evidence that K V 10.1 localizes to the centrosome and the primary cilium and promotes ciliary disassembly. Interference with K V 10.1 ciliary localization abolishes not only the effects on ciliary disassembly, but also K V 10.1-induced tumor progression in vivo. Conversely, upon knockdown of K V 10.1, ciliary disassembly is impaired, proliferation is delayed, and proliferating cells show prominent primary cilia. Thus, modulation of ciliogenesis by K V 10.1 can explain the influence of K V 10.1 expression on the proliferation of normal cells and is likely to be a major mechanism underlying its tumorigenic effects. Synopsis This study shows that K V 10.1 voltage-gated potassium channels localize to the centrosome/primary cilium, where they participate in ciliary disassembly. Abnormal expression decouples the ciliary cycle from the cell cycle, explaining the pro-tumorigenic effects of the channel. Functional expression of the K V 10.1 K + channel accelerates primary cilium disassembly Absence of K V 10.1 allows maintenance of cilia in proliferating cells. Overexpression or increased channel function leads to deciliation and induces developmental defects and tumorigenesis. This study shows that KV10.1 voltage-gated potassium channels localize to the centrosome/primary cilium, where they participate in ciliary disassembly. Abnormal expression decouples the ciliary cycle from the cell cycle, explaining the pro-tumorigenic effects of the channel.