Chapter Four - Structural and signaling role of lipids in plasma membrane repair

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Abstract

The plasma membrane forms the physical barrier between the cytoplasm and extracellular space, allowing for biochemical reactions necessary for life to occur. Plasma membrane damage needs to be rapidly repaired to avoid cell death. This relies upon the coordinated action of the machinery that polarizes the repair response to the site of injury, resulting in resealing of the damaged membrane and subsequent remodeling to return the injured plasma membrane to its pre-injury state. As lipids comprise the bulk of the plasma membrane, the acts of injury, resealing, and remodeling all directly impinge upon the plasma membrane lipids. In addition to their structural role in shaping the physical properties of the plasma membrane, lipids also play an important signaling role in maintaining plasma membrane integrity. While much attention has been paid to the involvement of proteins in the membrane repair pathway, the role of lipids in facilitating plasma membrane repair remains poorly studied. Here we will discuss the current knowledge of how lipids facilitate plasma membrane repair by regulating membrane structure and signaling to coordinate the repair response, and will briefly note how lipid involvement extends beyond plasma membrane repair to the tissue repair response.

Introduction

The plasma membrane separates the extracellular environment from the cell interior, where biochemical reactions necessary for life occur. The plasma membrane is semi-permeable, allowing the cell to communicate with and utilize resources from its surrounding environment. However, all cells are susceptible to plasma membrane damage, which results in the mixture of the intracellular and extracellular milieu and can result in death if the damage is not rapidly repaired. Plasma membrane repair relies on the coordinated activity of repair machinery, which carries out membrane fusion, membrane shedding, and polymerization of F-actin at the site of repair (Horn & Jaiswal, 2018). Repair of injured cells is tied closely to tissue repair and regeneration, as shown by studies demonstrating release of inflammatory mediators, including small molecules, peptides and proteins that signal to cells in the inflammatory and regenerative systems to initiate a tissue level reparative response.

The most abundant component of the cell's plasma membrane is the lipids. Lipids are a class of biomolecules, which are generally insoluble in water, and may refer to fatty acids, sterols, mono-, di-, and triglycerides, as well as phospholipids, among others. While with their ability to store energy, lipids are often ascribed a metabolic role, they also play important structural and signaling roles in the cell. Acute and chronic release of lipids and free fatty acids following cell and tissue injury has been widely recognized to be involved in the process of tuning the inflammatory and subsequent tissue repair response. Being the most abundant component of the plasma membrane, lipids are also an essential player in the process of plasma membrane repair; however, much of the research committed to identifying the mechanisms of plasma membrane repair has focused on the proteins associated with plasma membrane repair (Cooper & McNeil, 2015).

Lipids contribute to cellular physiology at both an individual and population level. Individual lipids can serve as signaling molecules on their own or through binding proteins, and chemical changes to a single lipid can initiate change in local membrane composition. At the population level, the composition of lipids in a membrane can result in formation of signaling platforms that can change the properties of an entire membrane, enabling the cell to finely tune tension, shape, and rigidity. At each of these levels the structural and signaling aspects of lipids are critical for the cell to mount an efficient response to plasma membrane injury. In this review, we will focus on the role of lipids during plasma membrane repair by discussing their functions as both structural and signaling molecules. We will highlight how lipids respond to injury and facilitate repair both at the level of individual molecules and at the bulk level by collectively altering the plasma membrane form and function.

Section snippets

Plasma membrane lipid composition, organization, and response to injury

The plasma membrane has a unique lipid composition that helps distinguish its structural and functional properties from the other internal membrane-bound compartments. Plasma membrane lipids can be grouped into three classes—glycerophospholipids, sphingolipids, and sterols. Each of these lipids contributes their own qualities that affect the structural and signaling characteristics of the plasma membrane (Nicolson, 2014). In mammalian cells, lipids formed upon the phosphate and glycerol (e.g.,

Structural role for lipids during plasma membrane repair

The physical properties of the plasma membrane are governed in large part by the effect of lipid interactions at the population level. For example, lipid composition, distribution, and inter-lipid interactions actively control the rigidity and tension acting upon the plasma membrane, which in turn regulates cellular functions such as vesicle fusion, cell motility, and membrane resealing (Diz-Muñoz, Fletcher, & Weiner, 2013; Gauthier, Fardin, Roca-Cusachs, & Sheetz, 2011; Togo, Krasieva, &

Signaling role for lipids during plasma membrane repair

For plasma membrane repair to occur successfully, the cell must possess a means to sense that injury has occurred, coordinate the change in activity and localization of repair machinery, and ultimately close the wounded area. To achieve these tasks, cells employ signaling networks, which respond to the changing microenvironment after injury and activate the diverse plasma membrane repair mechanisms with precise control in time and space. The structural role of lipids described above illustrates

Lipids as a mediator of tissue repair

Failure of injured cells to repair results in cell death and activates a tissue repair response. Despite the many different types of tissue, there is a common repair program involved in tissue repair. This involves a series of distinct, but mutually dependent stages including inflammation, regeneration, and remodeling of the tissue (Gurtner, Werner, Barrandon, & Longaker, 2008). Use of lipidomics during epidermal wound repair identified that several of the plasma membrane lipids discussed above

Conclusion

While often considered to be a passive resident of the plasma membrane, there is ample evidence to support a more active role of lipids in the process of plasma membrane repair as well as tissue repair. In this review, we have discussed how lipids working at the individual as well as at the population level facilitate the proper orchestration of the repair response. These roles of lipids in plasma membrane repair include both a structural role and a signaling role. Rather than these roles being

Acknowledgments

J.K.J. and A.H. acknowledge NIH for financial support—NIAMS (R01AR055686) and NICHD (U54HD090257) and thank our lab members for useful discussions and inputs during the course of writing and editing this work.

References (126)

  • E.M. Houang et al.

    Membrane-stabilizing copolymers confer marked protection to dystrophic skeletal muscle in vivo

    Molecular Therapy-Methods & Clinical Development

    (2015)
  • R.F. Jacob et al.

    Lipid peroxidation induces cholesterol domain formation in model membranes

    Journal of Biological Chemistry

    (2005)
  • J.L. Johnson et al.

    C-terminal di-arginine motif of Cdc42 protein is essential for binding to phosphatidylinositol 4, 5-bisphosphate-containing membranes and inducing cellular transformation

    Journal of Biological Chemistry

    (2012)
  • M.M. Kozlov et al.

    Membrane tension and membrane fusion

    Current Opinion in Structural Biology

    (2015)
  • M. Labazi et al.

    The antioxidant requirement for plasma membrane repair in skeletal muscle

    Free Radical Biology and Medicine

    (2015)
  • E. Ligeti et al.

    Phospholipids can switch the GTPase substrate preference of a GTPase-activating protein

    Journal of Biological Chemistry

    (2004)
  • R.P. Mason et al.

    Effect of oxidative stress on membrane structure: Small-angle X-ray diffraction analysis

    Free Radical Biology and Medicine

    (1997)
  • A.K. McNeil et al.

    Requirement for annexin A1 in plasma membrane repair

    Journal of Biological Chemistry

    (2006)
  • A.H. Merrill

    Sphingolipids biochemistry of lipids, lipoproteins and membranes

    (2008)
  • P. Nassoy et al.

    Stressing caveolae new role in cell mechanics

    Trends in Cell Biology

    (2012)
  • T. Nebl et al.

    Membrane cytoskeleton: PIP2 pulls the strings

    Current Biology

    (2000)
  • G.L. Nicolson

    The fluid—Mosaic model of membrane structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years

    Biochimica et Biophysica Acta (BBA)-Biomembranes

    (2014)
  • S. Potez et al.

    Tailored protection against plasmalemmal injury by annexins with different Ca2 + sensitivities

    Journal of Biological Chemistry

    (2011)
  • B. Ramstedt et al.

    Sphingolipids and the formation of sterol-enriched ordered membrane domains

    Biochimica et Biophysica Acta (BBA)-Biomembranes

    (2006)
  • A. Reddy et al.

    Plasma membrane repair is mediated by Ca2 +−regulated exocytosis of lysosomes

    Cell

    (2001)
  • A. Remorino et al.

    Gradients of Rac1 nanoclusters support spatial patterns of Rac1 signaling

    Cell Reports

    (2017)
  • A.N. Roach et al.

    Phosphatidic acid regulation of PIPKI is critical for actin cytoskeletal reorganization

    Journal of Lipid Research

    (2012)
  • Y. Senju et al.

    Regulation of actin dynamics by PI (4, 5) P2 in cell migration and endocytosis

    Current Opinion in Cell Biology

    (2019)
  • G.-Q. Bi et al.

    Calcium-regulated exocytosis is required for cell membrane resealing

    The Journal of Cell Biology

    (1995)
  • F. Bianco et al.

    Acid sphingomyelinase activity triggers microparticle release from glial cells

    The EMBO Journal

    (2009)
  • Bittel, D.,& Jaiswal, J. K. (2019). Contribution of extracellular vesicles in rebuilding injured muscles. Frontiers in...
  • A. Bouter et al.

    Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair

    Nature Communications

    (2011)
  • T.L. Boye et al.

    Annexin A4 and A6 induce membrane curvature and constriction during cell membrane repair

    Nature Communications

    (2017)
  • J.M. Braughler et al.

    Involvement of lipid peroxidation in CNS injury

    Journal of Neurotrauma

    (1992)
  • C. Cai et al.

    MG53 nucleates assembly of cell membrane repair machinery

    Nature Cell Biology

    (2009)
  • P.J. Casey

    Protein lipidation in cell signaling

    Science

    (1995)
  • R. Cazzolli et al.

    Phospholipid signalling through phospholipase D and phosphatidic acid

    IUBMB Life

    (2006)
  • M. Cebecauer et al.

    Membrane lipid nanodomains

    Chemical Reviews

    (2018)
  • J.P. Cheng et al.

    Caveolae protect endothelial cells from membrane rupture during increased cardiac output

    The Journal of Cell Biology

    (2015)
  • X. Cong et al.

    Plasma membrane wounding and repair in pulmonary diseases

    American Journal of Physiology-Lung Cellular and Molecular Physiology

    (2017)
  • S.T. Cooper et al.

    Membrane repair: Mechanisms and pathophysiology

    Physiological Reviews

    (2015)
  • M. Corrotte et al.

    Caveolae internalization repairs wounded cells and muscle fibers

    eLife

    (2013)
  • J. Dai et al.

    Regulation of endocytosis, exocytosis, and shape by membrane tension

  • S. Das et al.

    Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of membrane translocation and mechanism for polarized signaling

    Proceedings of the National Academy of Sciences

    (2015)
  • O. Daumke et al.

    Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling

    Nature

    (2007)
  • A. Defour et al.

    Dysferlin regulates cell membrane repair by facilitating injury-triggered acid sphingomyelinase secretion

    Cell Death & Disease

    (2014)
  • A.R. Demonbreun et al.

    An actin-dependent annexin complex mediates plasma membrane repair in muscle

    The Journal of Cell Biology

    (2016)
  • W. Do Heo et al.

    PI (3, 4, 5) P3 and PI (4, 5) P2 lipids target proteins with polybasic clusters to the plasma membrane

    Science

    (2006)
  • K.M. Eyster

    The membrane and lipids as integral participants in signal transduction: Lipid signal transduction for the non-lipid biochemist

    Advances in Physiology Education

    (2007)
  • N.C. Gauthier et al.

    Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading

    Proceedings of the National Academy of Sciences

    (2011)
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