Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication
- University of California, San Francisco, United States
- Howard Hughes Medical Institute, Boston Children's Hospital, United States
- United Arab Emirates University, United Arab Emirates
- University of Vienna, Austria
- Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States
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.
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Human subjects: Subjects were identified and evaluated in a clinical setting for medical history, cognitive impairment and physical abnormalities. Peripheral blood samples were collected from the affected individuals and family members after obtaining written informed consent according to the protocols approved by the participating institutions and the ethical standards of the responsible national and institutional committees on human subject research.
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© 2015, Kodani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication
eLife 4:e07519.
https://doi.org/10.7554/eLife.07519
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