The SNARE complex formed by RIC-4/SEC-22/SYX-2 promotes C. elegans epidermal wound healing
Qingfang Shao,
Chandra Sugiarto Wijaya,
Shen Wang,
Xinan Meng,
Cheng Yuan,
Cong Ma,
Suhong Xu
Affiliations
Qingfang Shao
International Biomedicine-X Research Center of the Second Affiliated Hospital, Zhejiang University School of Medicine and the Zhejiang University-University of Edinburgh Institute, 718 East Haizhou Road, Haining, Zhejiang 314400, China; Center for Stem Cell and Regenerative Medicine and Department of Burn and Wound Repair of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
Chandra Sugiarto Wijaya
International Biomedicine-X Research Center of the Second Affiliated Hospital, Zhejiang University School of Medicine and the Zhejiang University-University of Edinburgh Institute, 718 East Haizhou Road, Haining, Zhejiang 314400, China; School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
Shen Wang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Xinan Meng
International Biomedicine-X Research Center of the Second Affiliated Hospital, Zhejiang University School of Medicine and the Zhejiang University-University of Edinburgh Institute, 718 East Haizhou Road, Haining, Zhejiang 314400, China; School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
Cheng Yuan
International Biomedicine-X Research Center of the Second Affiliated Hospital, Zhejiang University School of Medicine and the Zhejiang University-University of Edinburgh Institute, 718 East Haizhou Road, Haining, Zhejiang 314400, China
Cong Ma
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Corresponding author
Suhong Xu
International Biomedicine-X Research Center of the Second Affiliated Hospital, Zhejiang University School of Medicine and the Zhejiang University-University of Edinburgh Institute, 718 East Haizhou Road, Haining, Zhejiang 314400, China; Center for Stem Cell and Regenerative Medicine and Department of Burn and Wound Repair of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Corresponding author
Summary: Maintaining cellular viability relies on the integrity of the plasma membrane, which must be repaired upon damage. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion is a crucial mechanism involved in membrane repair. In C. elegans epidermal cell hyp 7, syntaxin-2 (SYX-2) facilitates large membrane wound repair; however, the underlying molecular mechanism remains unclear. Here, we found that SNAP-25 protein RIC-4 and synaptobrevin protein SEC-22 are required for SYX-2 recruitment at the wound site. They interact to form a SNARE complex to promote membrane repair in vivo and fusion in vitro. Moreover, we found that SEC-22 localized in multiple intracellular compartments, including endosomes and the trans-Golgi network, which recruited to the wounds. Furthermore, inhibition of RAB-5 disrupted SEC-22 localization and prevented its interaction with SYX-2. Our findings suggest that RAB-5 facilitates the formation of the RIC-4/SEC-22/SYX-2 SNARE complex and provides valuable insights into the molecular mechanism of how cells repair large membrane wounds.
