Cilia and cell cycle re-entry

Kim, Sehyun; Tsiokas, Leonidas

doi:10.4161/cc.10.16.17009

Cited by 126 publications

(106 citation statements)

References 92 publications

(133 reference statements)

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“…Interestingly, deficiency of CDK10/CycM also delays both cilia disassembly and cell cycle re-entry in response to mitogenic signaling. In view of recent studies with several other ciliogenesis regulators, 33 it seems likely that the prolonged maintenance of primary cilia is acting to delay cell cycle entry, not vice versa.…”

Section: Discussionmentioning

confidence: 99%

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STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis

et al. 2016

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CDK10/CycM is a protein kinase deficient in STAR (toe Syndactyly, Telecanthus and Anogenital and Renal malformations) syndrome, which results from mutations in the X-linked FAM58A gene encoding Cyclin M. The biological functions of CDK10/CycM and etiology of STAR syndrome are poorly understood. Here, we report that deficiency of CDK10/Cyclin M promotes assembly and elongation of primary cilia. We establish that this reflects a key role for CDK10/Cyclin M in regulation of actin network organization, which is known to govern ciliogenesis. In an unbiased screen, we identified the RhoA-associated kinase PKN2 as a CDK10/ CycM phosphorylation substrate. We establish that PKN2 is a bone fide regulator of ciliogenesis, acting in a similar manner to CDK10/CycM. We discovered that CDK10/Cyclin M binds and phosphorylates PKN2 on threonines 121 and 124, within PKN2 0 s core RhoA-binding domain. Furthermore, we demonstrate that deficiencies in CDK10/CycM or PKN2, or expression of a non-phosphorylatable version of PKN2, destabilize both the RhoA protein and the actin network architecture. Importantly, we established that ectopic expression of RhoA is sufficient to override the induction of ciliogenesis resulting from CDK10/CycM knockdown, indicating that RhoA regulation is critical for CDK10/CycM's negative effect on ciliogenesis. Finally, we show that kidney sections from a STAR patient display dilated renal tubules and abnormal, elongated cilia. Altogether, these results reveal CDK10/CycM as a key regulator of actin dynamics and a suppressor of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling. Moreover, they suggest that STAR syndrome is a ciliopathy.

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Section: Discussionmentioning

confidence: 99%

“…28,[31][32][33] Thus, to investigate whether CDK10/CycM silencing modulates cilium disassembly and cell cycle re-entry, we took cells that had been treated with control, CDK10, CycM siRNAs and serum-starved for 72 hours (as in Fig. 1), and then reexposed them to serum for 14 hours.…”

Section: Cdk10/cycm Negatively Regulates Ciliogenesis and Primary Cilmentioning

confidence: 99%

STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis

et al. 2016

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“…60 It has been proposed that the primary cilium may function as a "physical checkpoint" for cell cycle re-entry since its resorption is apparently required for quiescence exit. 61 Might the microtubule intranuclear bundle assembled in S. cerevisiae be the distant cousin of the primary cilium?…”

Section: Microtubule And/or Centromere Attachment and The Fitness Ofmentioning

confidence: 99%

Microtubules move the nucleus to quiescence

Laporte

Sagot

2014

Nucleus

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T he nucleus is a cellular compartment that hosts several macro-molecular machines displaying a highly complex spatial organization. This tight architectural orchestration determines not only DNA replication and repair but also regulates gene expression. In budding yeast microtubules play a key role in structuring the nucleus since they condition the Rabl arrangement in G1 and chromosome partitioning during mitosis through their attachment to centromeres via the kinetochore proteins. Recently, we have shown that upon quiescence entry, intranuclear microtubules emanating from the spindle pole body elongate to form a highly stable bundle that spans the entire nucleus. Here, we examine some molecular mechanisms that may underlie the formation of this structure. As the intranuclear microtubule bundle causes a profound re-organization of the yeast nucleus and is required for cell survival during quiescence, we discuss the possibility that the assembly of such a structure participates in quiescence establishment.

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“…C'est une structure dynamique présente dans les cellules en phase G0 dont la formation et la résorption sont étroitement liées au cycle cellulaire [2,5,6]. Cette dynamique et le renouvellement des éléments constitutifs du cil sont assurés par un système de transport intra-ciliaire appelé IFT pour intraflagellar transport qui transporte de manière antérograde et rétrograde des complexes cargos via des protéines motrices [7,8].…”

Section: Le Cil Primaire Les Ciliopathies Et Leurs Traits Cliniquesunclassified