Title:Annexins Bend Wound Edges during Plasma Membrane Repair
Volume: 27
Issue: 22
Author(s): Adam Cohen Simonsen*, Theresa Louise Boye and Jesper Nylandsted*
Affiliation:
- Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK- 5230 Odense M,Denmark
- Membrane Integrity Group, Unit for Cell Death and Metabolism, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Strandboulevarden 49, DK- 2100 Copenhagen,Denmark
Keywords:
Annexin, plasma membrane repair, membrane curvature, membrane injury, cancer, annexin A4,
annexin A6.
Abstract: The plasma membrane of eukaryotic cells defines the boundary to the extracellular environment
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, reorganization
of cytoskeleton and membrane fusion events to reseal the membrane. Members of the
annexin protein family, which are characterized by their Ca2+-dependent binding to anionic phospholipids,
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 Ca2+ ions into the cytoplasm trigger recruitment of annexins
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.
