Abstract

Repair of wounds to individual cells is crucial for organisms to survive daily physiological or environmental stresses, as well as pathogen assaults, which disrupt the plasma membrane. Sensing wounds, resealing membranes, closing wounds and remodelling plasma membrane/cortical cytoskeleton are four major steps that are essential to return cells to their pre-wounded states. This process relies on dynamic changes of the membrane/cytoskeleton that are indispensable for carrying out the repairs within tens of minutes. Studies from different cell wound repair models over the last two decades have revealed that the molecular mechanisms of single cell wound repair are very diverse and dependent on wound type, size, and/or species. Interestingly, different repair models have been shown to use similar proteins to achieve the same end result, albeit sometimes by distinctive mechanisms. Recent studies using cutting edge microscopy and molecular techniques are shedding new light on the molecular mechanisms during cellular wound repair. Here, we describe what is currently known about the mechanisms underlying this repair process. In addition, we discuss how the study of cellular wound repair—a powerful and inducible model—can contribute to our understanding of other fundamental biological processes such as cytokinesis, cell migration, cancer metastasis and human diseases.

Highlights

  • Cells have been observed to repair major disruptions to their plasma membranes for over a century, and the capacity for self-repair is fundamental to an organism’s robustness [1,2,3,4,5,6,7]

  • We focus on the most recent findings in the field of single cell wound repair, with the goal of connecting these disparate developments to broader studies of different processes in basic science, as well as the pathology of certain human diseases

  • It has been proposed that this membranous patch attaches to the plasma membrane first at discrete points around the periphery of the wound, followed by complete ‘vertex fusion’ to seal the wound

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Summary

Introduction

Cells have been observed to repair major disruptions to their plasma membranes for over a century, and the capacity for self-repair is fundamental to an organism’s robustness [1,2,3,4,5,6,7]. Mounting evidence suggests that this may not occur in all cases as some cells appear to use mechanisms involving endocytosis/exocytosis (figure 1c) [8,9,10,15,18,19], and more recently it has been shown in Xenopus oocytes that a population of vesicles at the site of the wound are violently exocytosed, and resultant membrane fusions reseal the membrane hole [20] Following this immediate ‘triage’, cellular wounds are repaired by constriction of the membrane and underlying cortical cytoskeleton followed by remodelling of the cell cortex, which returns the wounded site to its pre-wounded state (figure 1d) [2,21,22,23]. We focus on the most recent findings in the field of single cell wound repair, with the goal of connecting these disparate developments to broader studies of different processes in basic science, as well as the pathology of certain human diseases

How does a cell perceive that it has been wounded?
Initiating events of cell wound repair: calcium influx
Initiating events of cell wound repair: oxidation
Initiating events of cell wound repair: other models
Re-sealing the membrane breach
Membrane ‘patch’ hypothesis
Other plugging mechanisms
Membrane plugging: insight from dysferlin and annexin studies
Cytoskeletal responses in cell wound repair
Rho family GTPase patterning primes assembly of wound repair players
Divergent mechanisms in actin ring translocation: actomyosin ring contraction
Divergent mechanisms in actin ring translocation: actin treadmilling
Membrane and cortical cytoskeleton remodelling
Beyond cellular repair
Future perspectives
56. Paluch EK et al 2015 Mechanotransduction: use the
65. Corrotte M et al 2013 Caveolae internalization
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