Myosin-Va is required for preciliary vesicle transportation to the mother centriole during ciliogenesis

Wu, Chi-Chang; Chen, Hsin‐Yi; Tang, Tang K.

doi:10.1038/s41556-017-0018-7

Cited by 109 publications

(160 citation statements)

References 52 publications

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“…In particular, satellites are required for centrosomal actin nucleation through targeting actin assembly factors to the centrosome . Satellites might also function in other actin‐regulated ciliary processes, such as periciliary vesicle transport to the basal body and cilia length regulation . Moreover, we also found a markedly strong increase at the protein level in neurogenesis‐linked pathways, such as neuronal body and extensions, postsynaptic membrane, and axon guidance.…”

Section: Discussionmentioning

confidence: 63%

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

et al. 2019

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Centriolar satellites are ubiquitous in vertebrate cells. They have recently emerged as key regulators of centrosome/cilium biogenesis, and their mutations are linked to ciliopathies. However, their precise functions and mechanisms of action remain poorly understood. Here, we generated a kidney epithelial cell line ( IMCD 3) lacking satellites by CRISPR /Cas9‐mediated PCM 1 deletion and investigated the cellular and molecular consequences of satellite loss. Cells lacking satellites still formed full‐length cilia but at significantly lower numbers, with changes in the centrosomal and cellular levels of key ciliogenesis factors. Using these cells, we identified new ciliary functions of satellites such as regulation of ciliary content, Hedgehog signaling, and epithelial cell organization in three‐dimensional cultures. However, other functions of satellites, namely proliferation, cell cycle progression, and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites affects transcription scarcely, but significantly alters the proteome. Importantly, the centrosome proteome mostly remains unaltered in the cells lacking satellites. Together, our findings identify centriolar satellites as regulators of efficient cilium assembly and function and provide insight into disease mechanisms of ciliopathies.

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Section: Discussionmentioning

confidence: 63%

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

et al. 2019

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“…However, actin filaments have been directly observed at the poles of mitotic spindles (Stevenson et al , ; Chodagam et al , ) and at the centrosome of several cell types in interphase (Farina et al , ; Obino et al , ; Au et al , ). Centrosomal actin filaments have been shown to anchor the centrosome to the nucleus (Bornens, ; Burakov & Nadezhdina, ; Obino et al , ), support the transport of vesicles during ciliogenesis (Assis et al , ; Wu et al , ), connect basal bodies to the actin cortex in ciliated cells (Pan et al , ; Antoniades et al , ; Walentek et al , ; Mahuzier et al , ) and power centrosome splitting in prophase (Uzbekov et al , ; Wang et al , ; Au et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…The centrosome is the main microtubule nucleating and organizing centre of the cell and sustains the highest concentration of microtubules in the cell. Centrosomal actin filaments have been shown to be involved in several functions including centrosome anchoring to the nucleus (Obino et al , ), centrosome separation in mitosis (Au et al , ) and ciliary‐vesicle transport in the early stages of ciliogenesis (Wu et al , ). Whether centrosomal actin filaments affect centrosomal microtubules is not yet known.…”

Section: Introductionmentioning

confidence: 99%

Actin filaments regulate microtubule growth at the centrosome

et al. 2019

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The centrosome is the main microtubule‐organizing centre. It also organizes a local network of actin filaments. However, the precise function of the actin network at the centrosome is not well understood. Here, we show that increasing densities of actin filaments at the centrosome of lymphocytes are correlated with reduced amounts of microtubules. Furthermore, lymphocyte activation resulted in disassembly of centrosomal actin and an increase in microtubule number. To further investigate the direct crosstalk between actin and microtubules at the centrosome, we performed in vitro reconstitution assays based on (i) purified centrosomes and (ii) on the co‐micropatterning of microtubule seeds and actin filaments. These two assays demonstrated that actin filaments constitute a physical barrier blocking elongation of nascent microtubules. Finally, we showed that cell adhesion and cell spreading lead to lower densities of centrosomal actin, thus resulting in higher microtubule growth. We therefore propose a novel mechanism, by which the number of centrosomal microtubules is regulated by cell adhesion and actin‐network architecture.

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“…Next, we used myosin Va accumulation at the CEP164‐marked mother centriole as an indication of preciliary vesicle transportation . In hCDC14A PD cells without serum starvation, the intensity of myosin Va vesicles surrounding the CEP164‐marked basal body was slightly higher in comparison with DBN1 KO RPE1 and RPE1 WT cells (Fig C and D).…”

Section: Resultsmentioning

confidence: 99%

The human phosphatase CDC 14A modulates primary cilium length by regulating centrosomal actin nucleation

et al. 2018

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CDC14A codes for a conserved proline‐directed phosphatase, and mutations in the gene are associated with autosomal‐recessive severe to profound deafness, due to defective kinocilia. A role of CDC14A in cilia formation has also been described in other organisms. However, how human CDC14A impacts on cilia formation remains unclear. Here, we show that human RPE1 hCDC14APD cells, encoding a phosphatase dead version of hCDC14A, have longer cilia than wild‐type cells, while hCDC14A overexpression reduces cilia formation. Phospho‐proteome analysis of ciliated RPE1 cells identified actin‐associated and microtubule binding proteins regulating cilia length as hCDC14A substrates, including the actin‐binding protein drebrin. Indeed, we find that hCDC14A counteracts the CDK5‐dependent phosphorylation of drebrin at S142 during ciliogenesis. Further, we show that drebrin and hCDC14A regulate the recruitment of the actin organizer Arp2 to centrosomes. In addition, during ciliogenesis hCDC14A also regulates endocytosis and targeting of myosin Va vesicles to the basal body in a drebrin‐independent manner, indicating that it impacts primary cilia formation in a multilayered manner.

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Myosin-Va is required for preciliary vesicle transportation to the mother centriole during ciliogenesis

Cited by 109 publications

References 52 publications

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

Actin filaments regulate microtubule growth at the centrosome

The human phosphatase CDC 14A modulates primary cilium length by regulating centrosomal actin nucleation

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