Cyclic expression of the voltage-gated potassium channel KV10.1 promotes disassembly of the primary cilium.
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. KV10.1 is a voltage-gated potassium channel frequently overexpressed in tumors. We have previously reported that expression of KV10.1 is temporally restricted to a time period immediately prior to mitosis in healthy cells. Here, we provide microscopical and biochemical evidence that KV10.1 localizes to the centrosome and the primary cilium and promotes ciliary disassembly. Interference with KV10.1 ciliary localization abolishes not only the effects on ciliary disassembly, but also KV10.1-induced tumor progression in vivo Conversely, upon knockdown of KV10.1, ciliary disassembly is impaired, proliferation is delayed, and proliferating cells show prominent primary cilia. Thus, modulation of ciliogenesis by KV10.1 can explain the influence of KV10.1 expression on the proliferation of normal cells and is likely to be a major mechanism underlying its tumorigenic effects.
Oncophysiology Group, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
Araceli
A
Sánchez
Oncophysiology Group, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
Diana
D
Urrego
Oncophysiology Group, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany pardo@em.mpg.de.
Luis A
0000-0003-1375-4349
LA
Pardo
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D018385:Centrosome; D002923:Cilia / Q000378:metabolism*; D051356:Cortactin / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
D051356:Cortactin; D051638:Ether-A-Go-Go Potassium Channels; D053823:Hedgehog Proteins; D034741:RNA, Small Interfering
KV10.1; cell cycle; primary cilium