1. Cell Biology
  2. Developmental Biology
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Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication

  1. Andrew Kodani
  2. Timothy W Yu
  3. Jeffrey R Johnson
  4. Divya Jayaraman
  5. Tasha L Johnson
  6. Lihadh Al-Gazali
  7. Lāszló Sztriha
  8. Jennifer N Partlow
  9. Hanjun Kim
  10. Alexis L Krup
  11. Alexander Dammermann
  12. Nevan Krogan
  13. Christopher A Walsh
  14. Jeremy F Reiter  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Howard Hughes Medical Institute, Boston Children's Hospital, United States
  3. United Arab Emirates University, United Arab Emirates
  4. University of Vienna, Austria
  5. Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States
Research Article
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Cite this article as: eLife 2015;4:e07519 doi: 10.7554/eLife.07519

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.

Article and author information

Author details

  1. Andrew Kodani

    Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Timothy W Yu

    Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jeffrey R Johnson

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Divya Jayaraman

    Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Tasha L Johnson

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lihadh Al-Gazali

    Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
    Competing interests
    The authors declare that no competing interests exist.
  7. Lāszló Sztriha

    Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
    Competing interests
    The authors declare that no competing interests exist.
  8. Jennifer N Partlow

    Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Hanjun Kim

    Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Alexis L Krup

    Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Alexander Dammermann

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  12. Nevan Krogan

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Christopher A Walsh

    Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Jeremy F Reiter

    Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    For correspondence
    Jeremy.Reiter@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

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.

Reviewing Editor

  1. W James Nelson, Stanford University, United States

Publication history

  1. Received: March 18, 2015
  2. Accepted: August 21, 2015
  3. Accepted Manuscript published: August 22, 2015 (version 1)
  4. Accepted Manuscript updated: August 24, 2015 (version 2)
  5. Accepted Manuscript updated: September 2, 2015 (version 3)
  6. Version of Record published: September 18, 2015 (version 4)

Copyright

© 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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