Cell shape and contractility regulate ciliogenesis in cell cycle–arrested cells

Pitaval, Amandine; Tseng, Qingzong; Bornens, Michel; Théry, Manuel

doi:10.1083/jcb.201004003

Cited by 190 publications

(212 citation statements)

References 29 publications

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“…In contrast, confined cells can organize a dorsal protrusive actin network, which promotes ciliogenesis. 13 Consistent with these observations, nucleating factors that promote actin polymerization repress primary cilium assembly and growth whereas actin severing enzymes promote ciliogenesis. [14][15][16][17] Actin depolymerization promotes ciliogenesis by stabilizing the pericentrosomal preciliary compartment, a vesiculotubular structure that contributes to ciliogenesis, 14,15,17 and by inhibiting transcription factors from the Hippo pathway, which induce the expression of cilium disassembly factors.…”

Section: Introductionsupporting

confidence: 71%

“…13,22,23 PKN2 0 s N-terminal domain is known to mediate its interaction with RhoA. 39 Thus, we hypothesized that CDK10/CycM might target this region, presumably in manner that would enhance RhoA and PKN2 0 s function in actin polymerization.…”

Section: Cdk10/cycm Maintains Rhoa Stability Through Pkn2 Phosphorylamentioning

confidence: 99%

“…20,21 In contrast, in monociliated cells, activation of RhoA and its downstream signaling pathway has been shown to suppress primary ciliogenesis by promoting the formation of actin stress fiber networks. 13,22,23 The presence of abnormal ciliogenesis and/ or abnormal primary cilium length during development has been linked to severe developmental syndromes, collectively dubbed ciliopathies. 11,24 Notably, hyperactivation of RhoA and consequent changes in actin polymerization have been observed in several prototypical ciliopathies, including Bardet-Biedl, Meckel and Joubert syndromes.…”

Section: Introductionmentioning

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: Introductionsupporting

confidence: 71%

Section: Cdk10/cycm Maintains Rhoa Stability Through Pkn2 Phosphorylamentioning

confidence: 99%

Section: Introductionmentioning

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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“…Interestingly, Tg737 orpk mice show defects in wound closure (36). Recent studies have shown that spatial constraint and actin cytoskeleton remodeling can control cilia elongation and resorption (37). It is tempting to speculate that mechanical forces generated during tissue patterning and disrupted by an injury can modulate the cellular response to cilia-mediated signaling by controlling primary cilia dynamics.…”

Section: Lentiviral-mediated Ift88rnai Phenocopies Tg737 Orpk Defectsmentioning

confidence: 99%

Primary cilia dynamics instruct tissue patterning and repair of corneal endothelium

Blitzer

Panagis

Gusella

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Primary cilia are required for several signaling pathways, but their function in cellular morphogenesis is poorly understood. Here we show that emergence of an hexagonal cellular pattern during development of the corneal endothelium (CE), a monolayer of neural crest-derived cells that maintains corneal transparency, depends on a precise temporal control of assembly of primary cilia that subsequently disassemble in adult corneal endothelial cells (CECs). However, cilia reassembly occurs rapidly in response to an in vivo mechanical injury and precedes basal body polarization and cellular elongation in mature CECs neighboring the wound. In contrast, CE from hypomorphic IFT88 mutants (Tg737 orpk ) or following in vivo lentiviral-mediated IFT88 knockdown display dysfunctional cilia and show disorganized patterning, mislocalization of junctional markers, and accumulation of cytoplasmic acetylated tubulin. Our results indicate an active role of cilia in orchestrating coordinated morphogenesis of CECs during development and repair and define the murine CE as a powerful in vivo system to study ciliary-based cellular dynamics. intraflagellar transport | eye development | ciliary length | microtubules

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“…Larger spread areas therefore cause cells to mimic a shape that would be seen in tissues that were stretched out. Such an increase in spread area also caused the cilia that were present to be shorter (Pitaval et al 2010). Suggesting that tensile forces, as with compressive forces, might inhibit ciliary formation.…”

Section: Mechanical Forces Affect Ciliogenesismentioning

confidence: 99%

Mechanobiology of Ciliogenesis

Ishikawa¹,

Marshall²

2014

BioScience

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Cilia are force-generating and -sensing organelles that serve as mechanical interfaces between the cell and the extracellular environment. Cilia are present in tissues that adaptively respond to mechanical loading and fluid flow, and defects in ciliary function can lead to diseases affecting these tissues. As might be expected for a mechanical interface, the formation of cilia is, itself, regulated by mechanical forces, and these links between mechanics and ciliary formation are providing new entry points for dissecting the regulatory pathways of ciliogenesis.

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Cell shape and contractility regulate ciliogenesis in cell cycle–arrested cells

Abstract: Adhesive micropatterns show the effect of spatial confinement and actin network architecture on basal body positioning and primary cilium formation.

Cited by 190 publications

References 29 publications

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

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

Primary cilia dynamics instruct tissue patterning and repair of corneal endothelium

Mechanobiology of Ciliogenesis

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