Titel
Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication
Autor*in
Andrew Kodani
Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco
Autor*in
Timothy W Yu
Howard Hughes Medical Institute, Boston Children's Hospital
Autor*in
Jeffrey R Johnson
Department of Cellular and Molecular Pharmacology, University of California, San Francisco
... show all
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.
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:447702
Erschienen in
Titel
eLife
Band
4
Verlag
eLife Sciences Organisation, Ltd.
Erscheinungsdatum
2015
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