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Elife. 2015 Aug 22;4. doi: 10.7554/eLife.07519.

Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.

Author information

1
Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
2
Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
3
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
4
Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
5
Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.

Abstract

Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication.

KEYWORDS:

brain development; cell biology; cell cycle; centriolar satellite; centriole; centrosome; developmental biology; human; microcephaly; stem cells

PMID:
26297806
PMCID:
PMC4574112
DOI:
10.7554/eLife.07519
[Indexed for MEDLINE]
Free PMC Article

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