CAMSAP2 organizes a γ-tubulin-independent microtubule nucleation centre through phase separation

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Abstract
Microtubules are dynamic polymers consisting of αβ-tubulin heterodimers. The initial polymerization process, called microtubule nucleation, occurs spontaneously via αβ-tubulin. Since a large energy barrier prevents microtubule nucleation in cells, the γ-tubulin ring complex is recruited to the centrosome to overcome the nucleation barrier. However, a considerable number of microtubules can polymerize independently of the centrosome in various cell types. Here, we present evidence that the minus-end-binding calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) serves as a strong nucleator for microtubule formation by significantly reducing the nucleation barrier. CAMSAP2 co-condensates with αβ-tubulin via a phase separation process, producing plenty of nucleation intermediates. Microtubules then radiate from the co-condensates, resulting in aster-like structure formation. CAMSAP2 localizes at the co-condensates and decorates the radiating microtubule lattices to some extent. Taken together, these in vitro findings suggest that CAMSAP2 supports microtubule nucleation and growth by organizing a nucleation centre as well as by stabilizing microtubule intermediates and growing microtubules.
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Funding Information
  • Japan Agency for Medical Research and Development (JP21gm0810013)
  • Japan Science and Technology Agency (JPMJPR14L2)
  • Moonshot Research and Development Program (JPMJMS2024)
  • Takeda Science Foundation
  • Mochida Memorial Foundation for Medical and Pharmaceutical Research
  • Uehara Memorial Foundation
  • Bristol-Myers Squibb
  • Hyogo Science and Technology Association
  • Japan Society for the Promotion of Science (KAKENHI 19K07246)
  • Japan Society for the Promotion of Science (KAKENHI 25221104)
  • Japan Society for the Promotion of Science (KAKENHI 19H03396)
  • Japan Society for the Promotion of Science (KAKENHI 21H05254)
  • Japan Agency for Medical Research and Development (JP21gm1610003)
  • FOREST Program (JPMJFR214K)

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