2. Academic Validation
  3. Decoupling actin assembly from microtubule disassembly by TBC1D3C-mediated direct GEF-H1 activation

Decoupling actin assembly from microtubule disassembly by TBC1D3C-mediated direct GEF-H1 activation

  • Life Sci Alliance. 2024 Oct 28;8(1):e202402585. doi: 10.26508/lsa.202402585.
Yi Luan 1 2 3 4,  Zhifeng Deng 1 2 3 4,  Yutong Zhu 5,  Lisi Dai 6 7,  Yang Yang 1,  Zongping Xia 8 2 3 4 9
Affiliations

Affiliations

  • 1 Clinical Systems Biology Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 2 Institute of Infection and Immunity, Henan Academy of Innovations in Medical Science, Zhengzhou, China.
  • 3 Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 4 NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 5 Research and Development Center, Beijing, China.
  • 6 Department of Pathology and Pathophysiology, and Department of Surgical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 7 School of Basic Medical Sciences, Zhejiang University, Hangzhou, China.
  • 8 Clinical Systems Biology Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China zxia2018@zzu.edu.cn.
  • 9 Life Sciences Institute, Zhejiang University, Hangzhou, China.
PMID: 39467635 DOI: 10.26508/lsa.202402585
Abstract

Actin and microtubules are essential cytoskeletal components and coordinate their dynamics through multiple coupling and decoupling mechanisms. However, how actin and microtubule dynamics are decoupled remains incompletely understood. Here, we identified TBC1D3C as a new regulator that can decouple actin filament assembly from microtubule disassembly. We showed that TBC1D3C induces the release of GEF-H1 from microtubules into the cytosol without perturbing microtubule arrays, leading to RhoA activation and actin filament assembly. Mechanistically, we found that TBC1D3C directly binds to GEF-H1, disrupting its interaction with the Tctex-DIC-14-3-3 complex and thereby displacing GEF-H1 from microtubules independently of microtubule disassembly. Super-resolution microscopy and live-cell imaging further confirmed that TBC1D3C triggers GEF-H1 release and actin filament assembly while maintaining microtubule integrity. Therefore, our findings demonstrated that TBC1D3C functions as a direct GEF activator and a novel regulator in decoupling actin assembly from microtubule disassembly, providing new insights into cytoskeletal regulation.

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