Annexin A7 is required for ESCRT III-mediated plasma membrane repair

Sci Rep. 2019 Apr 30;9(1):6726. doi: 10.1038/s41598-019-43143-4.

Stine Lauritzen Sønder ¹, Theresa Louise Boye ¹, Regine Tölle ² ³, Jörn Dengjel ² ³, Kenji Maeda ¹, Marja Jäättelä ¹ ⁴, Adam Cohen Simonsen ⁵, Jyoti K Jaiswal ⁶ ⁷, Jesper Nylandsted ⁸ ⁹

Affiliations

1 Unit for Cell Death and Metabolism, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
2 Department of Dermatology, Medical Center, University of Freiburg, 79104, Freiburg, Germany.
3 Department of Biology, University of Fribourg Chemin du Musée 10, 1700, Fribourg, Switzerland.
4 Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen N, Denmark.
5 Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230, Odense M, Denmark.
6 Children's National Health System, Center for Genetic Medicine Research, George Washington University School of Medicine and Health Sciences, 111 Michigan Avenue, NW, Washington, DC, 20010-2970, USA.
7 Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, 111 Michigan Avenue, NW, Washington, DC, 20010-2970, USA.
8 Unit for Cell Death and Metabolism, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. [email protected].
9 Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen N, Denmark. [email protected].

PMID: 31040365 DOI: 10.1038/s41598-019-43143-4

Abstract

The plasma membrane of eukaryotic cells forms the essential barrier to the extracellular environment, and thus plasma membrane disruptions pose a fatal threat to cells. Here, using invasive breast Cancer cells we show that the CA²⁺ - and phospholipid-binding protein annexin A7 is part of the plasma membrane repair response by enabling assembly of the endosomal sorting complex required for transport (ESCRT) III. Following injury to the plasma membrane and CA²⁺ flux into the cytoplasm, annexin A7 forms a complex with Apoptosis linked gene-2 (ALG-2) to facilitate proper recruitment and binding of ALG-2 and ALG-2-interacting protein X (ALIX) to the damaged membrane. ALG-2 and ALIX assemble the ESCRT III complex, which helps excise and shed the damaged portion of the plasma membrane during wound healing. Our results reveal a novel function of annexin A7 - enabling plasma membrane repair by regulating ESCRT III-mediated shedding of injured plasma membrane.

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