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The human phosphatase CDC 14A modulates primary cilium length by regulating centrosomal actin nucleation
Author(s) -
Uddin Borhan,
Partscht Patrick,
Chen NanPeng,
Neuner Annett,
Weiß Manuel,
Hardt Robert,
Jafarpour Aliakbar,
Heßling Bernd,
Ruppert Thomas,
Lorenz Holger,
Pereira Gislene,
Schiebel Elmar
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846544
Subject(s) - cilium , ciliogenesis , centrosome , microbiology and biotechnology , basal body , biology , phosphatase , microtubule , actin , phosphorylation , cell , genetics , gene , cell cycle , flagellum
CDC 14A 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 CDC 14A in cilia formation has also been described in other organisms. However, how human CDC 14A impacts on cilia formation remains unclear. Here, we show that human RPE 1 hCDC 14 A PD cells, encoding a phosphatase dead version of hCDC 14A, have longer cilia than wild‐type cells, while hCDC 14A overexpression reduces cilia formation. Phospho‐proteome analysis of ciliated RPE 1 cells identified actin‐associated and microtubule binding proteins regulating cilia length as hCDC 14A substrates, including the actin‐binding protein drebrin. Indeed, we find that hCDC 14A counteracts the CDK 5‐dependent phosphorylation of drebrin at S142 during ciliogenesis. Further, we show that drebrin and hCDC 14A regulate the recruitment of the actin organizer Arp2 to centrosomes. In addition, during ciliogenesis hCDC 14A 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.