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Title 

Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152

Authors 

T S KimJ E ParkA ShuklaS ChoiR N MuruganJ H LeeM AhnK RheeJ K BangBo Yeon KimJ LoncarekR L EriksonK S Lee

Publisher 

National Academy of Sciences

Issue Date 

2013

Citation 

Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 50, pp. e4849-e4857

Abstract 

Centrosomes play an important role in various cellular processes, including spindle formation and chromosome segregation. They are composed of two orthogonally arranged centrioles, whose duplication occurs only once per cell cycle. Accurate control of centriole numbers is essential for the maintenance of genomic integrity. Although it is well appreciated that polo-like kinase 4 (Plk4) plays a central role in centriole biogenesis, how it is recruited to centrosomes and whether this step is necessary for centriole biogenesis remain largely elusive. Here we showed that Plk4 localizes to distinct subcentrosomal regions in a temporally and spatially regulated manner, and that Cep192 and Cep152 serve as two distinct scaffolds that recruit Plk4 to centrosomes in a hierarchical order. Interestingly, Cep192 and Cep152 competitively interacted with the cryptic polo box of Plk4 through their homologous N-terminal sequences containing acidic-α-helix and N/Q-rich motifs. Consistent with these observations, the expression of either one of these N-terminal fragments was sufficient to delocalize Plk4 from centrosomes. Furthermore, loss of the Cep192- or Cep152-dependent interaction with Plk4 resulted in impaired centriole duplication that led to delayed cell proliferation. Thus, the spatiotemporal regulation of Plk4 localization by two hierarchical scaffolds, Cep192 and Cep152, is critical for centriole biogenesis.

ISSN 

0027-8424

Link 

http://dx.doi.org/10.1073/pnas.1319656110

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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