Human microcephaly protein CEP135 binds to hSAS-6 and CPAP, and is required for centriole assembly

Yu Chih Lin, Ching Wen Chang, Wen Bin Hsu, Chieh Ju C. Tang, Yi Nan Lin, En Ju Chou, Chien Ting Wu, Tang K. Tang

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


Centrioles are cylindrical structures that are usually composed of nine triplets of microtubules (MTs) organized around a cartwheel-shaped structure. Recent studies have proposed a structural model of the SAS-6-based cartwheel, yet we do not know the molecular detail of how the cartwheel participates in centriolar MT assembly. In this study, we demonstrate that the human microcephaly protein, CEP135, directly interacts with hSAS-6 via its carboxyl-terminus and with MTs via its amino-terminus. Unexpectedly, CEP135 also interacts with another microcephaly protein CPAP via its amino terminal domain. Depletion of CEP135 not only perturbed the centriolar localization of CPAP, but also blocked CPAP-induced centriole elongation. Furthermore, CEP135 depletion led to abnormal centriole structures with altered numbers of MT triplets and shorter centrioles. Overexpression of a CEP135 mutant lacking the proper interaction with hSAS-6 had a dominant-negative effect on centriole assembly. We propose that CEP135 may serve as a linker protein that directly connects the central hub protein, hSAS-6, to the outer MTs, and suggest that this interaction stabilizes the proper cartwheel structure for further CPAP-mediated centriole elongation.

Original languageEnglish (US)
Pages (from-to)1141-1154
Number of pages14
JournalEMBO Journal
Issue number8
StatePublished - Apr 17 2013
Externally publishedYes


  • cartwheel
  • centriole duplication
  • centrosome
  • microcephaly

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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