Insights & Perspectives The electric fence to cell-cycle progression: Do local changes in membrane potential facilitate disassembly of the primary cilium? Timely and localized expression of a potassium channel may set the conditions that allow retraction of the primary cilium Diana Urrego, Araceli S  anchez, Adam P. Tomczak and Luis A. Pardo * Kv10.1 is a voltage-gated potassium channel relevant for tumor biology, but the underlying mechanism is still unclear. We propose that Kv10.1 plays a role coordinating primary cilium disassembly with cell cycle progression through localized changes of membrane potential at the ciliary base. Most non-dividing cells display a primary cilium, an antenna-like structure important for cell physiology. The cilium is disassembled when the cell divides, which requires an increase of Ca 2þ concentration and a redistribution of phospholipids in its basal region, both of which would be facilitated by local hyperpolarization. Cells lacking Kv10.1 show impaired ciliary disassembly and delayed entrance into mitosis. Kv10.1 is predominantly expressed during G2/M, a critical period for ciliary resorption, and localizes to the ciliary base and vesicles associated with the centrosome. This could explain the influence of Kv10.1 in cell proliferation, as well as phenotypic features of patients carrying gain of function mutations in the gene. Keywords: .cancer; cell cycle; ion channel; membrane potential; PIP 2 ; primary cilium Introduction Most cells that are not actively dividing display a primary cilium, a solitary structure projecting into the environ- ment. Ignored for many decades, the relevance of the primary cilium as a signaling hub has awakened consider- able interest in the last years, and detailed reviews are regularly pub- lished (e.g. [1, 2]). We refer the reader to those for details, and will only describe briefly those features of the primary cilium relevant to the hypoth- esis we present. The primary cilium is a microtubule-based shaft sheathed into a membrane. Like in other cilia, the microtubule doublets of the primary cilium stem from a modified centriole, the basal body, which in this case corresponds to the mother centriole (the one of the two centrioles of the centrosome that was already present in the mother cell) tethered to the mem- brane through transition fibers (e.g. [3]). The centrosome is a complex organelle formed by mother and daughter cen- trioles embedded in a matrix of pro- teins called pericentriolar material (PCM) [4]. The close proximity between the primary cilium and the mother centriole and the PCM, allows that ciliary signals can be coupled to DOI 10.1002/bies.201600190 Max-Planck-Institut f€ ur experimentelle Medizin, AG Oncophysiology, G€ ottingen, Germany *Corresponding author: Luis A. Pardo E-mail: pardo@em.mpg.de Abbreviations: AURKA, Aurora A kinase; CaM, calmodulin; FGF, fibroblast growth factor; HEF1/NEDD9, human enhancer of filamentation 1/neural precursor cell expressed developmentally down-regulated protein 9; INPP5E, inositol 5-phosphatase; PDGF, platelet-derived growth factor; PIP 2 , phosphatidyl-inositol (4,5) bisphosphate; SHH, sonic hedgehog; WNT, wingless/int1. www.bioessays-journal.com 1600190 (1 of 6) Bioessays 39: 1600190, ß 2017 WILEY Periodicals, Inc. Ideas & Speculations