GCP6 is a substrate of Plk4 and required for centriole duplication.
Centriole duplication occurs once per cell cycle and requires Plk4, a member of the Polo-like kinase family. A key component of the centrosome is the γ-tubulin ring complex (γ-TuRC) that nucleates microtubules. GCP6 is a member of the γ-TuRC, but its role in human cells and the regulation of its functions remain unclear. Here we report that depletion of human GCP6 prevents assembly of the γ-TuRC and induces a high percentage of monopolar spindles. These spindles are characterized by a loss of centrosomal γ-tubulin and reduced centriole numbers. We found that GCP6 is localized in the pericentriolar material but also at distal portions of centrioles. In addition, GCP6 is required for centriole duplication and Plk4-induced centriole overduplication. GCP6 interacts with and is phosphorylated by Plk4. Moreover, we find that Plk4-dependent phosphorylation of GCP6 regulates centriole duplication. These data suggest that GCP6 is a target of Plk4 in centriole biogenesis.
Cell Cycle Control and Carcinogenesis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Ramona
R
Bahtz
Joerg
J
Seidler
Marc
M
Arnold
Uta
U
Haselmann-Weiss
Claude
C
Antony
Wolf D
WD
Lehmann
Ingrid
I
Hoffmann
D002460:Cell Line; D002502:Centrioles / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D008869:Microtubule-Associated Proteins; C444456:TUBGCP6 protein, human; D014404:Tubulin; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases