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. 2019 Oct 13;12(1):162-165.
doi: 10.1080/19420889.2019.1676139. eCollection 2019.

Annexins: Players of Single Cell Wound Healing and Regeneration

Free PMC article

Annexins: Players of Single Cell Wound Healing and Regeneration

Swantje Christin Häger et al. Commun Integr Biol. .
Free PMC article


Cell life is defined by a thin 4 nm plasma membrane, which separates the interior of a cell from its environment. Thus, disruption of the plasma membrane poses a critical risk to cells, which requires immediate repair to avoid uncontrolled osmotic lysis and cell death. The initial repair response to stop the leakage usually occurs within 10-45 s and implicates Ca2+-activated phospholipid-binding proteins including annexins. We previously reported that annexin-induced curvature of lateral membrane around the hole plays an important role for immediate resealing of human cancer cells. Once the breach has been sealed, the cell often regenerates itself by removing the damaged membrane. This process, which also involves annexins includes excision and shedding of damaged membrane implicating the endosomal sorting complex required for transport (ESCRT) III and actin cytoskeleton remodeling. Hence, studies of cell membrane repair mechanisms should differentiate between the immediate repair response happening within seconds and the subsequent regeneration phase, which occurs in the order of minutes to hours after injury.

Keywords: Plasma membrane repair; annexins; cell membrane; initial repair; regeneration; wound healing.


Figure 1.
Figure 1.
Model for plasma membrane repair in mammalian cells that discriminates between initial resealing and subsequent regeneration. Injury to the membrane and influx of Ca2+ ions into the cytoplasm activate annexin proteins that are recruited to the damaged membrane within 10-45 s. Here, ANXA4 and ANXA6 induce out-of-plane curvature and in-plane constriction, respectively, which in collaboration with other annexin family members enriches lateral membrane and promotes wound closure. Upon initial resealing, cells start to regenerate their membrane by shedding damaged membrane and/or by internalization (not shown). Excision of larger membrane areas requires F-actin buildup, which is regulated by ANXA2 protein at the injured membrane. Smaller membrane pieces are shedded in the form of ectosomes – a process that is facilitated by the ESCRT III complex. ANXA7 is needed to position and attach the ESCRT III components ALG-2 and ALG-2-interacting protein X (ALIX) at the injured membrane during this phase.

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Grant support

This work was partly funded by the Danish Council for Independent Research, Natural Sciences [6108-00378A], Scientific Committee Danish Cancer Society [R90-A5847-14-S2] (JN), and the Novo Nordisk Foundation [NNF18OC0034936].

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