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  The human phosphatase CDC14A modulates primary cilium length by regulating centrosomal actin nucleation

Uddin, B., Partscht, P., Chen, N.-P., Neuner, A., Weiss, M., Hardt, R., et al. (2019). The human phosphatase CDC14A modulates primary cilium length by regulating centrosomal actin nucleation. EMBO Reports, 20(1): e46544. doi:10.15252/embr.201846544.

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 Urheber:
Uddin, Borhan1, Autor
Partscht, Patrick1, Autor
Chen, Nan-Peng2, Autor           
Neuner, Annett1, Autor
Weiss, Manuel1, Autor
Hardt, Robert1, Autor
Jafarpour, Aliakbar1, Autor
Hessling, Bernd1, Autor
Ruppert, Thomas1, Autor
Lorenz, Holger1, Autor
Pereira, Gislene1, Autor
Schiebel, Elmar1, Autor
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Schlagwörter: CILIARY VESICLE DOCKING; MITOTIC EXIT; PROTEIN; CILIOGENESIS; IDENTIFICATION; APPENDAGES; REVEALS; C-NAP1Biochemistry & Molecular Biology; Cell Biology; actin; CDK5; DBN1; hCDC14A; primary cilium;
 Zusammenfassung: 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 hCDC14A(PD) 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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Sprache(n): eng - English
 Datum: 2018-11-222019-01
 Publikationsstatus: Erschienen
 Seiten: 16
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000459024800005
DOI: 10.15252/embr.201846544
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Titel: EMBO Reports
  Andere : EMBO Rep.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Oxford, UK : Published for EMBO by Oxford University Press
Seiten: - Band / Heft: 20 (1) Artikelnummer: e46544 Start- / Endseite: - Identifikator: ISSN: 1469-221X
CoNE: https://pure.mpg.de/cone/journals/resource/110978984569661