Primary Cilium Disassembly in Mammalian Cells Occurs Predominantly by Whole-Cilium Shedding

Abstract

AbstractThe primary cilium is a central signaling hub in cell proliferation and differentiation, and is built and disassembled every cell cycle in most animal cells. Disassembly is critically important: misregulation or delay of disassembly leads to cell cycle defects. The physical means by which cilia are disassembled are poorly understood, and thought to involve resorption of disassembled components into the cell body. To investigate cilium disassembly in mammalian cells, we used rapid live-cell imaging to comprehensively characterize individual disassembly events. The predominant mode of disassembly was rapid cilium loss via deciliation, in which the membrane and axoneme of the cilium was shed from the cell. Gradual resorption was also observed, as well as events in which a period of gradual resorption ended with rapid deciliation. Deciliation resulted in intact shed cilia that could be recovered from culture medium and contained both membrane and axoneme proteins. We modulated levels of katanin and intracellular calcium, two putative regulators of deciliation, and found that excess katanin promotes disassembly by deciliation, independently of calcium. Together, these results demonstrate that mammalian ciliary disassembly involves a tunable decision between deciliation and resorption.