Mechanism of ciliary disassembly

Abstract

As motile organelles and sensors, cilia play pivotal roles in cell physiology, development and organ homeostasis. Ciliary defects are associated with a class of cilia-related diseases or developmental disorders, termed ciliopathies. Even though the presence of cilia is required for diverse functions, cilia can be removed through ciliary shortening or resorption that necessitates disassembly of the cilium, which occurs normally during cell cycle progression, cell differentiation and in response to cellular stress. The functional significance of ciliary resorption is highlighted in controlling the G1-S transition during cell cycle progression. Internal or external cues that trigger ciliary resorption initiate signaling cascades that regulate several downstream events including depolymerization of axonemal microtubules, dynamic changes in actin and the ciliary membrane, regulation of intraflagellar transport and posttranslational modifications of ciliary proteins. To ensure ciliary resorption, both the active disassembly of the cilium and the simultaneous inhibition of ciliary assembly must be coordinately regulated.

Mechanisms of ciliogenesis suppression in dividing cells

“…One model is that ciliary length in quiescent cells may determine the G1 duration after cell-cycle reentry [30]. This model is supported by the following observations.…”

“…The majority of cells begin to retract their primary cilia at the cell-cycle reentry (the G0/G1 transition) [21–23, 27–30]. Since Tucker et al first reported the reciprocal relationship between ciliation and cell proliferation in cultured cells [27, 28], ciliary absorption (deciliation) has been well analyzed in cell culture [21, 29, 30]. To analyze the deciliation, cultured cells are typically starved of serum and then treated with serum or defined growth factors to induce deciliation.…”

“…Tucker et al first described the relationship between deciliation and cell-cycle progression: the deciliation after cell-cycle reentry appears to complete prior to DNA replication [accompanied with centriolar (centrosomal) duplication] [27, 28]. Since then, several researchers have reported that primary cilia are completely disassembled prior to the S or M phases [21, 23, 29, 30]. …”

“…However, some species reportedly retain their cilia during cell proliferation [30]. For example, many ciliated protozoans maintain their cortical cilia throughout cell division [37].…”

The Ciliopathy-Associated Cep104 Protein Interacts with Tubulin and Nek1 Kinase

“…Several kinases such as Aurora A, Plk1, and NIMA-related kinases such as Nek1 and Nek2 have been implicated in regulating the stability of cilia (Liang et al., 2016). Nek1 localizes to the basal body region (Shalom et al., 2008), and also to cilia when overexpressed as a kinase dead version (White and Quarmby, 2008).…”