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. Despite the many different types of tissue, there is a common repair program involved in tissue repair. Epub 2015 Oct 19. Similarly, peak PIP2 accumulation at the injury site occurred 45 seconds post-injury in Xenopus oocytes (Vaughan et al., 2014). Constitutive fusion of biosynthetic vesicles is a major mechanism for delivery of new lipids and proteins, which helps to build and maintain the plasma membrane. For example, membrane shedding is a known mechanism of plasma membrane repair, which functions to limit the lateral expansion of the wound area (Andrews, Almeida, & Corrotte, 2014; Horn & Jaiswal, 2018). These phospholipids are important for the formation of other molecules that are involved in cell signaling and help to bind proteins and carbohydrates to the outer cell membrane. 8600 Rockville Pike Int J Mol Sci. Charged phospholipids such as PIP2, PS, and PE are almost exclusively found on the inner leaflet, while the glycosphingolipids are only found on the outer leaflet. With their calcium and lipid affinities spanning a wide spectrum, annexins accumulate slightly differently from each other at the site of injury and perform different functions to facilitate repair of the wounded plasma membrane (see Section 4.1). doi: 10.3791/50848. The goal of signaling during plasma membrane repair is to generate a polarized response such that the repair machinery can be spatially and temporally localized and activated at the repair site. Cambridge (MA): Harvard Stem Cell Institute; 2008. The structural role of lipids described above illustrates how their ability to modify the biophysical properties of the plasma membrane is beneficial for resealing. Dysferlin is not detected at injury sites until 10 s postinjury, a delay we attribute to an intermediary step involving calpain cleavage. Gauthier NC, Masters TA, & Sheetz MP (2012). For example, shear force on the plasma membrane, such as that experienced during a mechanical injury, results in lipid mixing, which increases the mobility of signaling lipids and proteins residing in stable lipid microdomains (Petersen et al., 2016). Disclaimer. Accessibility Further, PA is implicated in processes critical to the success of membrane repair such as vesicle fusion with the plasma membrane and GTPase signaling (Cazzolli et al., 2006; Zhang & Du, 2009). A decrease in membrane tension precedes successful cell-membrane repair. Zuzek A, Fan JD, Spaeth CS, & Bittner GD (2013). A cartoon depicting the potential role of dysferlin-mediated vesicle fusion in membrane repair. Repair of muscle fibers lacking the dysferlin protein, which results in reduced membrane stability, is improved by the presence of extracellular (oxidized) MG53 protein, suggesting that this protein can act on the outer leaflet of the plasma membrane to improve plasma membrane in diseased cells. Cazzolli R, Shemon AN, Fang MQ, & Hughes WE (2006). Evidence suggests these pores are removed both by endosomal degradative pathways (123, 164, 280) and exosomal shedding (14, 118, 136). Trends Cell Biol. These enzymes initiate signaling through the generation of new lipid species, providing an added spatial, as well as a temporal component to lipid signaling, helping to more precisely coordinate the repair response. Another broad group of lipid carriers that are recognized for their role in activating stem cells are extracellular vesicles (EVs), which are released locally at the site of injury or from a distant site and through their lipid and other cargoes regulate regeneration of injured tissues by way of stem cell activation (Riazifar, Pone, Ltvall, & Zhao, 2017). Nojima H, Freeman CM, Gulbins E, & Lentsch AB (2015). Gurtner GC, Werner S, Barrandon Y, & Longaker MT (2008). Lysosome fusion is required for the process of repair (Reddy, Caler, & Andrews, 2001). The major differences between normal cells and cancer cells relate to growth, communication, cell repair and death, "stickiness" and spread, appearance, maturation, evasion of the immune system, function and blood supply . Direct lipid modification of proteins, such as GTPases, provides another method to regulate protein localization and activity (Casey, 1995). What is cell membrane integrity? - Studybuff PKC, in turn, influences a wide variety of downstream pathways known to facilitate repair including vesicle fusion, Rho GTPase patterning, as well as repair potentiation (Togo, 2004; Vaughan et al., 2014; Zuzek et al., 2013). This is due to their lack of integration into the membrane under normal lipid packing conditions. 8600 Rockville Pike Houang EM, Haman KJ, Filareto A, Perlingeiro RC, Bates FS, Lowe DA, & Metzger JM (2015). 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. However, these repair activities can also be observed at the single-cell level. While initial depolymerization of the local F-actin network is thought to assist with vesicle fusion and membrane shedding, delayed accumulation of F-actin may facilitate repair either by working in coordination with myosin to pull the wounded membrane edges toward each other or by providing a barrier and stabilizing function for the newly formed membrane. official website and that any information you provide is encrypted 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. How does the cell membrane self heal? The product of PC metabolism by PLD is the signaling lipid PA (Cazzolli, Shemon, Fang, & Hughes, 2006). Labazi M, McNeil AK, Kurtz T, Lee TC, Pegg RB, Angeli JPF, McNeil PL (2015). and transmitted securely. Mechanistically, the process of membrane shedding is mediated by the endosomal sorting complexes required for transport (ESCRT) proteins (Jimenez et al., 2014; Scheffer et al., 2014). sharing sensitive information, make sure youre on a federal Plasma membrane lipids are routinely interconverted as a means to maintain lipid homeostasis and for lipid-mediated signaling. Calcium also initiates lipid signaling after plasma membrane injury by activating phospholipases, such as phospholipase C (PLC). There also exists lateral heterogeneity of lipid composition within each leaflet, which is demonstrated by the formation of lipid microdomains, such as the sphingomyelin and cholesterol-rich domains that exist interspersed among the phospholipids throughout the plasma membrane (Cebecauer et al., 2018; Sezgin, Levental, Mayor, & Eggeling, 2017) (Figure 2B). There are many differences between cancer cells and normal cells in noncancerous (benign) or cancerous (malignant) tumors. 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). However, lipid signaling also helps to coordinate downstream repair pathways that result in the membrane trafficking and cytoskeletal reorganization required for repair. official website and that any information you provide is encrypted Endocytosis can also occur at sites of membrane invagination known as caveolae, and caveolae internalization has been implicated in membrane repair (Corrotte et al., 2013). Yet the membrane is also a formidable barrier, allowing some dissolved substances, or solutes, to pass while blocking others. Phosphatidic acid regulation of PIPKI is critical for actin cytoskeletal reorganization. We have briefly discussed how such an integral role of lipids in plasma membrane repair also extends into tissue-level repair and restoration of organ function. Verweij FJ, Revenu C, Arras G, Dingli F, Loew D, Pegtel DM, Zimmermann P (2019). Each month, well bring you a selection of compelling updates to this ever-growing library of biological strategies and innovations. Unauthorized use of these marks is strictly prohibited. PA is itself generated primarily from glycerol-3-phosphate, which is a product of glycolysis. Promotion of plasma membrane repair by vitamin E. Idone V, Tam C, Goss JW, Toomre D, Pypaert M, & Andrews NW (2008). In order to provide a cell with energy, these molecules have to pass across the cell membrane, which functions as a barrier but not an impassable one. Given their ability to traverse away from the site of synthesis (Verweij et al., 2019), the EVs generated during plasma membrane injury may activate both local and distant tissue regeneration responses needed for repair. Below we describe the biochemical signaling role of lipids in facilitating plasma membrane repair. This study showed that shear force on the membrane, as experienced by cells during mechanical injury, facilitated increased PLD activity through the process of lipid mixing. Cell damage (also known as cell injury) is a variety of changes of stress that a cell suffers due to external as well as internal environmental changes. 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. Biosci Rep. 2023 Feb 27;43(2):BSR20220765. Campelo F, Fabrikant G, McMahon HT, & Kozlov MM (2010). The plasma membrane, also called the cell membrane, is the membrane found in all cells that separates the interior of the cell from the outside environment. Das S, Yin T, Yang Q, Zhang J, Wu YI, & Yu J (2015). While it is unclear whether caveolae can provide structural assistance to the damaged membrane in the context of a large membrane injury (as opposed to sub-injury threshold stress, (Sinha et al., 2011)), caveolae may still provide a signaling function during the repair process. EVs are known to be generated in response to plasma membrane injury of single cells, and this is required for successful repair (Jimenez et al., 2014; Scheffer et al., 2014). 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.