Annexins Bend Wound Edges during Plasma Membrane Repair

Adam Cohen Simonsen*, Theresa Louise Boye, Jesper Nylandsted*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The plasma membrane of eukaryotic cells defines the boundary to the extracellular envi-ronment and, thus provides essential protection from the surroundings. Consequently, disruptions to the cell membrane triggered by excessive mechanical or biochemical stresses pose fatal threats to cells, which they need to cope with to survive. Eukaryotic cells cope with these threats by activating their plasma membrane repair system, which is shared by other cellular functions, and includes mechanisms to remove damaged membrane by internalization (endocytosis), shedding, re-organization of cytoskeleton and membrane fusion events to reseal the membrane. Members of the annexin protein family, which are characterized by their Ca 2+-dependent binding to anionic phos-pholipids, are important regulators of plasma membrane repair. Recent studies based on cellular and biophysical membrane models show that they have more distinct functions in the repair response than previously assumed by regulating membrane curvature and excision of damaged membrane. In cells, plasma membrane injury and flux of Ca 2+ ions into the cytoplasm trigger recruitment of annex-ins including annexin A4 and A6 to the membrane wound edges. Here, they induce curvature and constriction force, which help pull the wound edges together for eventual fusion. Cancer cells are dependent on efficient plasma membrane repair to counteract frequent stress-induced membrane injuries, which opens novel avenues to target cancer cells through their membrane repair system. Here, we discuss mechanisms of single cell wound healing implicating annexin proteins and membrane curvature.

Original languageEnglish
JournalCurrent Medicinal Chemistry
Volume27
Issue number22
Pages (from-to)3600-3610
ISSN0929-8673
DOIs
Publication statusPublished - 2020

Bibliographical note

(E-pub Ahead of Print)

Keywords

  • Annexin
  • Annexin A4
  • Annexin A6
  • Cancer
  • Membrane curvature
  • Membrane injury
  • Plasma membrane repair
  • Cell Membrane
  • Calcium
  • Phospholipids
  • Wound Healing
  • Annexins
  • Cytoskeleton

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