title: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.
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.
authors: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
authors: Andrew
authors: A
authors: Kodani
authors: Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
authors: Timothy W
authors: TW
authors: Yu
authors: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
authors: Jeffrey R
authors: JR
authors: Johnson
authors: Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
authors: Divya
authors: D
authors: Jayaraman
authors: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
authors: Tasha L
authors: TL
authors: Johnson
authors: Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors: Lihadh
authors: L
authors: Al-Gazali
authors: Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors: Lāszló
authors: L
authors: Sztriha
authors: Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
authors: Jennifer N
authors: JN
authors: Partlow
authors: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
authors: Hanjun
authors: H
authors: Kim
authors: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
authors: Alexis L
authors: AL
authors: Krup
authors: Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
authors: Alexander
authors: A
authors: Dammermann
authors: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
authors: Nevan J
authors: NJ
authors: Krogan
authors: Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
authors: Christopher A
authors: CA
authors: Walsh
authors: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
authors: Jeremy F
authors: JF
authors: Reiter
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055503:Protein Multimerization
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: brain development; cell biology; cell cycle; centriolar satellite; centriole; centrosome; developmental biology; human; microcephaly; stem cells