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Cep57 regulates human centrosomes through multivalent interactions.
Yeh, Hung-Wei; Chen, Po-Pang; Yeh, Tzu-Chen; Lin, Shiou-Lan; Chen, Yue-Ting; Lin, Wan-Ping; Chen, Ting; Pang, Jia Meng; Lin, Kai-Ti; Wang, Lily Hui-Ching; Lin, Yu-Chun; Shih, Orion; Jeng, U-Ser; Hsia, Kuo-Chiang; Cheng, Hui-Chun.
Afiliación
  • Yeh HW; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Chen PP; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Yeh TC; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Lin SL; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Chen YT; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Lin WP; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Chen T; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Pang JM; Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Lin KT; Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Wang LH; Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Lin YC; Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Shih O; National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.
  • Jeng US; National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.
  • Hsia KC; Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Cheng HC; Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
Proc Natl Acad Sci U S A ; 121(25): e2305260121, 2024 Jun 18.
Article en En | MEDLINE | ID: mdl-38857398
ABSTRACT
Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Centrosoma / Proteínas Asociadas a Microtúbulos / Microtúbulos Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Centrosoma / Proteínas Asociadas a Microtúbulos / Microtúbulos Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos