2. Academic Validation
  3. CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72

CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72

  • BMC Biol. 2022 Oct 24;20(1):240. doi: 10.1186/s12915-022-01437-6.
Zhenguang Ying 1,  Kaifang Wang 1,  Junfeng Wu 1,  Mingyu Wang 2,  Jing Yang 1,  Xia Wang 1,  Guowei Zhou 3,  Haibin Chen 4,  Hongwu Xu 5 6,  Stephen Cho Wing Sze 7 8,  Feng Gao 9,  Chunman Li 10 11,  Ou Sha 12 13
Affiliations

Affiliations

  • 1 Department of Anatomy, Histology and Developmental Biology, Shenzhen University Health Science Centre, Shenzhen, 518000, China.
  • 2 Medical AI Laboratory, School of Biomedical Engineering, Shenzhen University Health Science Centre, Shenzhen, 518000, China.
  • 3 Shenzhen University Health Science Centre, Shenzhen, 518000, China.
  • 4 Department of Histology and Embryology, Shantou University Medical College, Shantou, 515000, China.
  • 5 Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515000, China.
  • 6 Department of Clinically Oriented Anatomy, Shantou University Medical College, Shantou, 515000, China.
  • 7 Department of Biology, Faculty of Science, Hong Kong Baptist University, Hongkong, 999077, China.
  • 8 Golden Meditech Centre for NeuroRegeneration Sciences, Hong Kong Baptist University, Hongkong, 999077, China.
  • 9 School of Dentistry, Shenzhen University Health Science Centre, Shenzhen, 518000, China.
  • 10 Department of Anatomy, Shantou University Medical College, Shantou, 515000, China. [email protected].
  • 11 Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, 515000, China. [email protected].
  • 12 Department of Anatomy, Histology and Developmental Biology, Shenzhen University Health Science Centre, Shenzhen, 518000, China. [email protected].
  • 13 School of Dentistry, Shenzhen University Health Science Centre, Shenzhen, 518000, China. [email protected].
PMID: 36280838 DOI: 10.1186/s12915-022-01437-6
Abstract

Background: The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored.

Results: We found that HCR interacts directly with astrin, a key factor in centrosome maturation and mitosis. Immunoprecipitation assays showed that the coiled-coil region present in the C-terminus of HCR and astrin respectively mediated the interaction between them. Astrin not only recruits HCR to the centrosome, but also protects HCR from ubiquitin-proteasome-mediated degradation. In addition, depletion of either HCR or astrin significantly reduced centrosome localization of CEP72 and subsequent MCPH proteins, including CEP152, CDK5RAP2, and CEP63. The absence of HCR also caused centriole duplication defects and mitotic errors, resulting in multipolar spindle formation, genomic instability, and DNA damage.

Conclusion: We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.

Keywords

Astrin; CCHCR1; CEP72; Centrosome; Microtubule organization; Mitosis.

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