While intracellular MG53 is a redox-sensitive protein capable of facilitating vesicle aggregation, it is proposed to have multiple functions during membrane repair. "Think of a . The signaling lipid PS is interesting in this regard due to its localization to the wound edge after injury. 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-Muoz, Fletcher, & Weiner, 2013; Gauthier, Fardin, Roca-Cusachs, & Sheetz, 2011; Togo, Krasieva, & Steinhardt, 2000). Shao S, Liao X, Xie F, Deng S, Liu X, Ristaniemi T, & Liu B (2018). In bacterial and plant cells, a cell wall is attached to the plasma membrane on its outside surface. In fact, cells are able to perform hundreds, even thousands, of chemical transformations at the same time under life-friendly conditions (ambient temperature and pressure in an aqueous environment). Just like cells have membranes to hold everything in, these mini-organs are also bound in a double layer of phospholipids to insulate their little compartments within the larger cells. Survival from bacterial pore-forming toxins utilizes both exocytic and endocytic responses. However, these repair activities can also be observed at the single-cell level. However, to successfully repair the cell also needs to restore the barrier function of the resealed membrane. During the G1 stage, the cell prepares for division by increasing its mass. Within a single leaflet, lateral heterogeneity is found in the form of lipid microdomains, such as the cholesterol and sphingolipid-rich domains that serve as signaling platforms to accumulate plasma membrane-associated proteins. Membrane proteins also help locally shape and provide rigidity to the plasma membrane by interacting with specific lipids or lipid domains (Cebecauer et al., 2018). The plasma membrane forms the physical barrier between the cytoplasm and extracellular space, allowing for biochemical reactions necessary for life to occur. Sphingolipids in liver injury, repair and regeneration, Development of Biomimetic Membrane Assemblies on Microspheres for High-Throughput and Multiplexable Studies, Caveolae as plasma membrane sensors, protectors and organizers. 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. To regulate the composition of plasma membrane lipids, cells utilize vesicle trafficking, which can add lipids (by exocytosis) or remove lipids (by endocytosis) from the plasma membrane. Van Meer G, Voelker DR, & Feigenson GW (2008). Cell Calcium. Spontaneous resealing of plasma membrane, Spontaneous resealing of plasma membrane injuries in the nanometer range is opposed by, Calcium-activated exocytosis reduces membrane tension, Calcium-activated exocytosis reduces membrane tension and promotes spontaneous repair driven by lipid disorder, Very large plasma membrane disruptions (micron diameter) require membrane patching. Dystrophic heart failure blocked by membrane sealant poloxamer, Cytosolic proteins can exploit membrane localization to trigger functional assembly, Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement, Phosphatidic acid signaling regulation of Ras superfamily of small guanosine triphosphatases, Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. Ligeti E, Dagher M-C, Hernandez SE, Koleske AJ, & Settleman J (2004). This lipid binds ALIX and is capable of budding vesicles away from the cytosol (Matsuo et al., 2004). Injury to the plasma membrane also changes the biochemical environment within the cell. EHD2 localization at caveolae results from its affinity for phosphatidylinositol 4,5-bisphosphate (PIP2), which is enriched around the caveolae boundary (Parton & Del Pozo, 2013; Simone, Caplan, & Naslavsky, 2013). Thus, DAG acts as a scaffold that initiates and coordinates downstream signaling pathways within a tight spatial and temporal window rather than as a marker of membrane injury for fast-acting structural proteins. Lateral movement, rotation, and flipping of lipids between the leaflets of the plasma membrane are the physical changes that work together to allow the fluid membrane to adapt to the changes in membrane tension (Nicolson, 2014) (Figure 2C). An official website of the United States government. Repeated eccentric exercise in healthy subjects (i.e., stepping down for 20 min) is known to induce damage so severe that muscle fibers degenerate over the following days and weeks (91, 131, 199). Poloxamer 188 facilitates the repair of alveolus resident cells in ventilator-injured lungs, American journal of respiratory and critical care medicine. Sci Rep. 2023 Mar 23;13(1):4763. doi: 10.1038/s41598-023-31973-2. Modular, cascade-like transcriptional program of regeneration in, R01 GM113602/GM/NIGMS NIH HHS/United States. This study showed that endocytosis occurs after membrane resealing and is mediated by the CLIC/GEEC pathway effector GRAF1, which is implicated in repair of muscle fiber plasma membrane injury (Lenhart et al., 2015). Zuzek A, Fan JD, Spaeth CS, & Bittner GD (2013). Collective evidence reveals membrane repair employs primitive yet robust molecular machinery, such as vesicle fusion and contractile rings, processes evolutionarily honed for simplicity and success. Bacterial pore-forming toxins oligomerize and insert in the plasma membrane of target cells forming a diffusible pore. sharing sensitive information, make sure youre on a federal Regulation of actin binding proteins by PIP2 occurs in part through electrostatic interactions (Senju et al., 2017), suggesting that clusters of PIP2 molecules may be necessary to achieve build-up of F-actin itself. The plasma membrane consists of a lipid bilayer that is semipermeable. 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. Glycerol-3-phosphate is used to generate PA as well as PG through the intermediate phosphatidylglycerol phosphate (PGP). One of the roles of lipid mobility may be to allow for the movement of individual lipids to form microdomains near the site of injury, which has been shown to be important for repair (Vaughan et al., 2014), perhaps by facilitating lipid-mediated signaling. Requirement for annexin A1 in plasma membrane repair, Repairing a torn cell surface: make way, lysosomes to the rescue, Plasma membrane disruption: repair, prevention, adaptation, Annual review of cell and developmental biology, Coping with the inevitable: how cells repair a torn surface membrane, Biochemistry of lipids, lipoproteins and membranes. 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. It must repair itself, first by stopping the loss of cytoplasm, and then regenerate by rebuilding structures that were damaged or lost. Epub 2008 Mar 3. Lysosomes are involved with various cell processes. Riazifar M, Pone EJ, Ltvall J, & Zhao W (2017). Not only is the composition and organization of the plasma membrane in constant flux, the membrane itself also must interact with forces being applied to it from all directions. 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. The second stage of tissue repair, regeneration, makes use of signaling by different lipids, one of which is sphingolipid. While being a mostly non-polar molecule, owing to its steroid backbone and hydrocarbon chain, cholesterol does possess a hydroxyl group opposite the hydrocarbon chain. All of the above mechanisms for regulating the physical properties of the membrane play important roles in determining how a cell responds to plasma membrane injury and undergoes successful repair. 2015 Sep;45:2-9. doi: 10.1016/j.semcdb.2015.09.023. The .gov means its official. Another endogenous mechanism of acutely decreasing membrane lipid mobility after injury involves the lipid species ceramide, the formation of which causes endocytosis in response to membrane injury through the activity of extracellular acid sphingomyelinase (Tam et al., 2010). The physical and molecular mechanisms by which a cell can heal membrane ruptures and rebuild damaged or missing cellular structures remain poorly understood. Similar to PLC, phospholipase D (PLD) activity is also increased after injury and is required for repair (Arun et al., 2013). Eukaryotic cells have been shown to utilize calcium-activated exocytosis to reduce membrane tension and promote repair via lipid-disorder driven attractions. Houang EM, Haman KJ, Filareto A, Perlingeiro RC, Bates FS, Lowe DA, & Metzger JM (2015). The calcium influx of a membrane injury activates vesicular exocytosis and homo- and heterotypic fusion of cytoplasmic vesicles. In addition to working on their own, lipids also interact with proteins to coordinate these processes. S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells, S100 and annexin proteins identify cell membrane damage as the Achilles heel of metastatic cancer cells. In general, PIP2 is a positive regulator of F-actin polymerization and the presence of PIP2 increases the stability of the actin cytoskeletonplasma membrane interface. Drescher DG, Drescher MJ, Selvakumar D, Annam NP. Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding? The site is secure. Like the exterior walls of a house, the . Because membrane tension limits the ability of cellular membranes to self-seal, cellular mechanisms that reduce membrane tension can promote membrane sealing. Cell Regen. Instead, distinct inter- and intra-leaflet heterogeneity exists. Transient and local lipid peroxidation may affect membrane stabilization as peroxidation of polyunsaturated fatty acids changes head group separation and acyl chain interdigitation, increasing their molecular volume and causing formation of distinct cholesterol domains in the membrane, which increases the membrane rigidity (Jacob & Mason, 2005; Mason, Walter, & Mason, 1997). Following this, accumulation of Annexin 4 and Annexin 6 results in folding and inward contraction of the injured membrane, respectively (Boye et al., 2017). The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Clipboard, Search History, and several other advanced features are temporarily unavailable. Inclusion in an NLM database does not imply endorsement of, or agreement with, lipids) is one of the roles proposed for lysosome-mediated repair (Andrews et al., 2014; McNeil, 2002). Miyake K, McNeil PL, Suzuki K, Tsunoda R, & Sugai N (2001). Stem cell extracellular vesicles: extended messages of regeneration, Annual review of pharmacology and toxicology. Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. Similarly, peak PIP2 accumulation at the injury site occurred 45 seconds post-injury in Xenopus oocytes (Vaughan et al., 2014). HHS Vulnerability Disclosure, Help The precise role of EHD2 in membrane repair is not known, although it is known as a membrane shaping protein that may be involved in membrane fusion (Campelo, Fabrikant, McMahon, & Kozlov, 2010).
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