PT  - JOURNAL ARTICLE
AU  - Luan, Yi
AU  - Deng, Zhifeng
AU  - Zhu, Yutong
AU  - Dai, Lisi
AU  - Yang, Yang
AU  - Xia, Zongping
TI  - Decoupling actin assembly from microtubule disassembly by TBC1D3C-mediated direct GEF-H1 activation
AID  - 10.26508/lsa.202402585
DP  - 2025 Jan 01
TA  - Life Science Alliance
PG  - e202402585
VI  - 8
IP  - 1
4099  - https://www.life-science-alliance.org/content/8/1/e202402585.short
4100  - https://www.life-science-alliance.org/content/8/1/e202402585.full
SO  - Life Sci. Alliance2025 Jan 01; 8
AB  - 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.Further information on materials, datasets, and protocols should be directed to zxia2018{at}zzu.edu.cn.