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

• Published in: Scientific reports Vol. 9; no. 1; p. 6726
• Main Authors: Sønder, Stine Lauritzen, Boye, Theresa Louise, Tölle, Regine, Dengjel, Jörn, Maeda, Kenji, Jäättelä, Marja, Simonsen, Adam Cohen, Jaiswal, Jyoti K., Nylandsted, Jesper
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.04.2019; Nature Publishing Group
• Subjects: 14; 14/19; 14/35; 631/57/2271; 631/67/1347; 631/80/313/2155; ALG-2-interacting protein; Annexin A7 - genetics; Annexin A7 - metabolism; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Breast cancer; Calcium-binding protein; Calcium-Binding Proteins - metabolism; Cell Cycle Proteins - metabolism; Cell Membrane - drug effects; Cell Membrane - metabolism; Cytoplasm; Digitonin - toxicity; Endosomal Sorting Complexes Required for Transport - metabolism; Female; HeLa Cells; Humanities and Social Sciences; Humans; Invasiveness; MCF-7 Cells; Membranes; multidisciplinary; Phospholipids; Plasma; Protein X; Science; Science (multidisciplinary); Wound healing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-43143-4

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 Ca 2+ - 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 Ca 2+ 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.