Cilia Disassembly with Two Distinct Phases of Regulation

Abstract

Cilia and flagella are dynamic organelles that undergo assembly and disassembly during each cell cycle. They are structurally polarized, and the mechanisms by which these organelles are disassembled are incompletely understood. Here, we show that flagellar resorption occurs in two distinct phases of length-dependent regulation. A CDK-like kinase, encoded by flagellar shortening 1 (FLS1), is required for the normal rate of disassembly of only the distal part of the flagellum. Mechanistically, loss of function of FLS1 prevents the initial phosphorylation of CALK, an aurora-like kinase that regulates flagellar shortening, and induces the earlier onset of the inhibitory phosphorylation of CrKinesin13, a microtubule depolymerase, which is involved in flagellar shortening. In addition, CALK and CrKinesin13 phosphorylation can also be induced by the process of flagellar shortening itself, demonstrating an example of cilia-generated signaling not requiring the binding of a ligand or the stimulation of an ion channel.

Functional exploration of the IFT-A complex in intraflagellar transport and ciliogenesis

“…Previously published protocols were followed [61]. For immunofluorescence, cells were fixedin4% paraformaldehyde, permeabilized with 0.5% NP40, resuspended in MT buffer, and attached to a 10 well slide previously coated with 0.1% polyethyleneimine and extracted with methanol at -20°C for 10 min.…”

Epithelial to Stromal Re-Distribution of Primary Cilia during Pancreatic Carcinogenesis

“…It has been reported that the length of cilia changes in conditions such as injury [44] or inflammation [45], influences cell cycle time [19, 46] and that shortening of PC induces a phosphorylation signaling cascade [47]. It has been therefore been speculated that the information of axonemal length may be sent into the cytosol and that this signal may be able to regulate the cell cycle re-entry [48], nominating PC as a tumor suppressor that potentially transmits cytostatic signals to the cell [39].…”

The Biology of Ciliary Dynamics

“…They also suggest that ciliary resorption is a novel checkpoint for G 1 -S transition (Kim and Tsiokas 2011; Sung and Li 2011). In support of this view, several molecules important for ciliary resorption, including Aurora A, HDAC6, centrosomal-P4.1-associated protein (CPAP), and FLS1/CKDL5, have been shown to be vital for cell-cycle progression (Li et al 2011; Hu et al 2015; Gabriel et al 2016). …”