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Mechanism of Ca2+-triggered ESCRT assembly and regulation of cell membrane repair

Author

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  • Luana L. Scheffer

    (Children's National Medical Center, Center for Genetic Medicine Research)

  • Sen Chandra Sreetama

    (Children's National Medical Center, Center for Genetic Medicine Research)

  • Nimisha Sharma

    (Children's National Medical Center, Center for Genetic Medicine Research
    Present address: University School of Biotechnology, G.G.S. Indraprastha University, Dwarka, New Delhi 110078, India)

  • Sushma Medikayala

    (Children's National Medical Center, Center for Genetic Medicine Research)

  • Kristy J. Brown

    (Children's National Medical Center, Center for Genetic Medicine Research
    George Washington University School of Medicine and Health Sciences)

  • Aurelia Defour

    (Children's National Medical Center, Center for Genetic Medicine Research)

  • Jyoti K. Jaiswal

    (Children's National Medical Center, Center for Genetic Medicine Research
    George Washington University School of Medicine and Health Sciences)

Abstract

In muscle and other mechanically active tissue, cell membranes are constantly injured, and their repair depends on the injury-induced increase in cytosolic calcium. Here, we show that injury-triggered Ca2+ increase results in assembly of ESCRT III and accessory proteins at the site of repair. This process is initiated by the calcium-binding protein—apoptosis-linked gene (ALG)-2. ALG-2 facilitates accumulation of ALG-2-interacting protein X (ALIX), ESCRT III and Vps4 complex at the injured cell membrane, which in turn results in cleavage and shedding of the damaged part of the cell membrane. Lack of ALG-2, ALIX or Vps4B each prevents shedding, and repair of the injured cell membrane. These results demonstrate Ca2+-dependent accumulation of ESCRT III-Vps4 complex following large focal injury to the cell membrane and identify the role of ALG-2 as the initiator of sequential ESCRT III-Vps4 complex assembly that facilitates scission and repair of the injured cell membrane.

Suggested Citation

  • Luana L. Scheffer & Sen Chandra Sreetama & Nimisha Sharma & Sushma Medikayala & Kristy J. Brown & Aurelia Defour & Jyoti K. Jaiswal, 2014. "Mechanism of Ca2+-triggered ESCRT assembly and regulation of cell membrane repair," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6646
    DOI: 10.1038/ncomms6646
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    Cited by:

    1. Tomoyuki Hatano & Saravanan Palani & Dimitra Papatziamou & Ralf Salzer & Diorge P. Souza & Daniel Tamarit & Mehul Makwana & Antonia Potter & Alexandra Haig & Wenjue Xu & David Townsend & David Rochest, 2022. "Asgard archaea shed light on the evolutionary origins of the eukaryotic ubiquitin-ESCRT machinery," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Yonglun Zeng & Baiying Li & Shuxian Huang & Hongbo Li & Wenhan Cao & Yixuan Chen & Guoyong Liu & Zhenping Li & Chao Yang & Lei Feng & Jiayang Gao & Sze Wan Lo & Jierui Zhao & Jinbo Shen & Yan Guo & Ca, 2023. "The plant unique ESCRT component FREE1 regulates autophagosome closure," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. B. Vijayalakshmi Ayyar & Khalil Ettayebi & Wilhelm Salmen & Umesh C. Karandikar & Frederick H. Neill & Victoria R. Tenge & Sue E. Crawford & Erhard Bieberich & B. V. Venkataram Prasad & Robert L. Atma, 2023. "CLIC and membrane wound repair pathways enable pandemic norovirus entry and infection," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Niccolò Mosesso & Niharika Savant Lerner & Tobias Bläske & Felix Groh & Shane Maguire & Marie Laura Niedermeier & Eliane Landwehr & Karin Vogel & Konstanze Meergans & Marie-Kristin Nagel & Malte Dresc, 2024. "Arabidopsis CaLB1 undergoes phase separation with the ESCRT protein ALIX and modulates autophagosome maturation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    5. Patrick Niekamp & Felix Scharte & Tolulope Sokoya & Laura Vittadello & Yeongho Kim & Yongqiang Deng & Elisabeth Südhoff & Angelika Hilderink & Mirco Imlau & Christopher J. Clarke & Michael Hensel & Ch, 2022. "Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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