The .gov means its official. Clipboard, Search History, and several other advanced features are temporarily unavailable. Honeybee immune systems depend more on protein diversity thanquantity. Once membrane tension is restored, the poloxamer compound is forced out of the outer membrane leaflet (Houang, Sham, Bates, & Metzger, 2018). Annexin A1 deficiency does not affect myofiber repair but delays regeneration of injured muscles. In addition to allowing for the lateral translocation of membrane lipids, injury-triggered increase in membrane fluidity also results in reduced lipid packing. Membrane lipids: where they are and how they behave. Yasuda S, Townsend D, Michele DE, Favre EG, Day SM, & Metzger JM (2005). Petersen EN, Chung H-W, Nayebosadri A, & Hansen SB (2016). We know first-hand some of the characteristics that make mammals unique, like having hair, being able to sweat, and producing milk through mammary glands. (2013). The plasma membrane is semi-permeable, allowing the cell to communicate with and utilize resources from its surrounding environment. Thus, caveolae may serve a signaling function during membrane repair (see Section 4). Slabodnick M, Prevo B, Gross P, Sheung J, Marshall W. J Vis Exp. Along with the annexins, which act quickly to physically manipulate the membrane itself, reassembly of the cytoskeleton plays a crucial role in restoring membrane tension in the later stages of repair. Interestingly, as a result of caveolae flattening, EHD2 dissociates from the plasma membrane and translocates to the nucleus where it alters gene transcription (Torrino et al., 2018). While PC exists in both the inner and outer leaflet of the plasma membrane, the charged phospholipids PE, PI, and PS are almost exclusively maintained within the inner leaflet (Nicolson, 2014; van Meer, 1989). 'Resealing' is the emergency response required for cell . Godin LM, Vergen J, Prakash Y, Pagano RE, & Hubmayr RD (2011). Federal government websites often end in .gov or .mil. Unable to load your collection due to an error, Unable to load your delegates due to an error, Spontaneous resealing of plasma membrane injuries in the nanometer range is opposed by the forces of the underlying membrane cytoskeleton. Cambridge (MA): Harvard Stem Cell Institute; 2008. Being the most abundant component of the plasma membrane, lipids are also 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). Thus, each of these lipids contributes significantly to the organization, structure, and function of the plasma membrane as a whole. 2021 Apr 2;19(1):63. doi: 10.1186/s12915-021-00970-0. Each of these provides another mechanism for generating specific membrane lipids acutely in parallel to biosynthetic inputs. Cazzolli R, Shemon AN, Fang MQ, & Hughes WE (2006). Lipids act as signaling molecules through their ability to directly bind or otherwise alter the activity or localization of target proteins (Figure 2B, ,C).C). 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. This lipid binds ALIX and is capable of budding vesicles away from the cytosol (Matsuo et al., 2004). 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 has since become evident that in addition to resealing, remodeling of the plasma membrane through vesicle fusion (exocytosis), vesicle internalization (endocytosis), and shedding (ectocytosis) also contribute to the repair process (reviewed in (Horn & Jaiswal, 2018)). Bissig C, Lenoir M, Velluz M-C, Kufareva I, Abagyan R, Overduin M, & Gruenberg J (2013). Spontaneous formation of a self-healing carbon nanoskin at the liquid-liquid interface. Ligeti E, Dagher M-C, Hernandez SE, Koleske AJ, & Settleman J (2004). Vaughan EM, You J-S, Yu H-YE, Lasek A, Vitale N, Hornberger TA, & Bement WM (2014). These roles of lipids in plasma membrane repair include both a structural role and a signaling role. Rapid actin-cytoskeletondependent recruitment of plasma membranederived dysferlin at wounds is critical for muscle membrane repair. The cell membrane is an extremely pliable structure composed primarily of two layers of phospholipids (a "bilayer"). Proc Natl Acad Sci U S A. For example, when humans receive a cut, they must limit blood loss. They consist of a variety of lipid mediators derived from the omega-3 essential fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and include lipoxins, resolvins and protectins. For example, PIP2 interacts with actin-associated proteins, resulting in a local strengthening of the plasma membrane-cytoskeleton interface. Cholesterol modulates cell signaling and protein networking by specifically interacting with PDZ domain-containing scaffold proteins. 2015 Sep;45:2-9. doi: 10.1016/j.semcdb.2015.09.023. However, uninjured muscle cells from Limb Girdle Muscular Dystrophy 2B (LGMD2B) patients show increased membrane fluidity, which is associated with their poor membrane repair ability (Sreetama et al., 2018). Endogenous mechanisms of repair in healthy cells appear to mimic the beneficial effect provided by poloxamer 188 by allowing for transient increases in lipid mobility while restricting fluidity increase to a relatively small spatial or temporal window. 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. However, all cells are susceptible to plasma membrane damage, which results in the mixture of the intracellular fluid and extracellular milieu and can result in death if the damage is not rapidly repaired. Cell walls provide structural support for the cell. The observation, that endocytosis may not be required for resealing through the removal of pore-forming toxins but instead acts as a mechanosensor to buffer membrane tension, may also explain how endocytosis participates in the repair of mechanical damage, where no membrane-spanning pores need to be removed. Biosci Rep. 2023 Feb 27;43(2):BSR20220765. Arp2/3-mediated F-actin formation controls regulated exocytosis in vivo. 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 form of membrane remodeling maintains lipid homeostasis and plasma membrane functionality. HHS Vulnerability Disclosure, Help Simone LC, Caplan S, & Naslavsky N (2013). From PA, cells generate DAG, or cytidine diphosphate-DAG (CDP-DAG), which serve as inputs into the phospholipid biosynthetic pathways (Figure 1A, ,B).B). While the structural importance of plasma membrane cholesterol is well appreciated, it can also play a role in signaling. Plasma membrane damage increases the fluidity of individual lipids, allowing them more freedom to migrate laterally, rotate, or even flip appearing in the opposite leaflet of the membrane. All RightsReserved. Jaiswal JK, Lauritzen SP, Scheffer L, Sakaguchi M, Bunkenborg J, Simon SM, Nylandsted J (2014). The basement membrane of the basal cells attaches via hemidesmosomes to the underlying Bowman's layer, while anchoring fibrils pass through . Thus, it is clear that there is a need to acknowledge the role of lipids as an active participant in the processes of both cell and tissue repair. This may allow these lipids and proteins to interact with new partners that were unavailable due to spatial segregation prior to injury. Marmots maintain strong bones during hibernation by building up without breakingdown. The variety of possible phospholipid interconversions, such as these, allows the cell to rapidly change the lipid composition of the plasma membrane. Pollet H, Conrard L, Cloos A-S, & Tyteca D (2018). Lenhart KC, ONeill TJ, Cheng Z, Dee R, Demonbreun AR, Li J, Taylor JM (2015). Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair. and transmitted securely. Thus, electrostatic interaction with signaling lipids helps to facilitate GTPase localization, which is a critical feature that determines the efficiency and magnitude of the downstream response (Das et al., 2015; Yogurtcu & Johnson, 2018). Inflammatory exudates provide insights into the regulation of the first stage of wound repair inflammation. They may be used to destroy invading viruses and bacteria. The plasma membrane has a unique lipid composition that helps distinguish its structural and functional properties from the other internal membrane-bound compartments. Mechanistic principles underlying regulation of the actin cytoskeleton by phosphoinositides, Regulation of actin dynamics by PI (4, 5) P2 in cell migration and endocytosis, Pro-resolving lipid mediators are leads for resolution physiology. FOIA For example, when inserted into a region abundant in phospholipids, cholesterol has a rigidifying effect; however, the opposite can be true with sphingolipids. Membrane damage: Damage to the cell membrane disturbs the state of cell electrolytes, e.g. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). (B) Phospholipid biosynthesis depends on multiple inputs from metabolism (glycerol-3-phosphate) and extracellular import (choline and ethanolamine). PI (3, 4, 5) P3 and PI (4, 5) P2 lipids target proteins with polybasic clusters to the plasma membrane, The membrane and lipids as integral participants in signal transduction: lipid signal transduction for the non-lipid biochemist. How does the cell membrane self heal? This process, facilitated by the dysferlin-mediated release of acid sphingomyelinase (Defour et al., 2014) creates microdomains of ceramide from sphingomyelin. The product of PC metabolism by PLD is the signaling lipid PA (Cazzolli, Shemon, Fang, & Hughes, 2006). An official website of the United States government. Sarcolemmal repair is a slow process and includes EHD2, Effect of oxidative stress on membrane structure: small-angle X-ray diffraction analysis. An organelle (think of it as a cell's internal organ) is a membrane bound structure found within a cell. This signaling function may occur due to the activity of the repair protein EHD2, which accumulates at the site of membrane injury and is thought to play a role in shaping membrane dynamics (Daumke et al., 2007; Demonbreun et al., 2016; Marg et al., 2012). Use of lipidomics during epidermal wound repair identified that several of the plasma membrane lipids discussed above are enriched during wound repair. sharing sensitive information, make sure youre on a federal McDade JR, Archambeau A, & Michele DE (2014). In addition to working on their own, lipids also interact with proteins to coordinate these processes. As a library, NLM provides access to scientific literature. PTRF presumably contributes to the translocation of MG53 to the injury-site, where MG53 is also able to bind PS and become activated in an oxidation-dependent manner (Cai et al., 2009). Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D, Conversion of phosphatidylcholine to phosphatidylglycerol with phospholipase D and glycerol, Journal of the American Oil Chemists Society. These same processes also work to dynamically control membrane fluidity by regulating the distribution of phospholipids, sphingolipids, and cholesterol in the membrane. For example, a scallop prevents structural failure from fracture because its shell is comprised of two materials of varying stiffness. Similar to PLC, phospholipase D (PLD) activity is also increased after injury and is required for repair (Arun et al., 2013). In contrast to PC, sphingomyelin forms a taller and narrower cylinder, which along with the configuration of its acyl chains, allowing this lipid to pack more tightly than phospholipids (Cebecauer et al., 2018). During regeneration, sphingolipids such as sphingosine 1-phosphate (S1P) are known for their growth promoting effect on tissue resident stem cells (Calise et al., 2012; Nojima, Freeman, Gulbins, & Lentsch, 2015). 2022 Aug 4;11:e80778. Healing of a punctured, The regeneration and reorganization of the oral apparatus (green) of, Wound healing studies in model cells such as. "Self-repair: Our bodies are packages within packages. The antioxidant requirement for plasma membrane repair in skeletal muscle. Muscle fibers have a, Schematic representation of the structural, Schematic representation of the structural features of the protein families implicated in membrane, A cartoon depicting the potential role of dysferlin-mediated vesicle fusion in membrane repair., MeSH With larger injuries, the opposing force of membrane tension exceeds the resealing forces of lipid disorder at the edges of the disruption, negating the driving forces of spontaneous membrane resealing. Yet to be fully understood is whether core membrane repair machinery exists in all cells, or whether evolutionary adaptation has resulted in multiple compensatory repair pathways that specialize in different tissues and cells within our body. (2017). Dr. Norma Andrews overviews the mechanisms of cellular plasma membrane repair. Bacterial pore-forming toxins oligomerize and insert in the plasma membrane of target cells forming a diffusible pore. PA is itself generated primarily from glycerol-3-phosphate, which is a product of glycolysis. Microfluidic guillotine reveals multiple timescales and mechanical modes of wound response in Stentor coeruleus. 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. Intriguingly, PIP2 is needed for PLD activity suggesting the possibility that a feed-forward loop leads to increasing PIP2 concentrations as repair progresses ultimately facilitating the necessary build-up of F-actin (Figure 1B). 2018 Apr 23;28(8):R392-R397. However, excessive force applied to the membrane can result in physical damage, such as the shear force applied on the endothelial cells by blood flow, on muscle cells during contraction, on lung alveolar cells during breathing, or by a blunt force trauma to any cell (Cong, Hubmayr, Li, & Zhao, 2017; Demonbreun & McNally, 2016; McNeil & Steinhardt, 2003). Annexins can physically manipulate the injured plasma membrane by stabilizing, folding, and contracting in order to facilitate repair (Gerke et al., 2005; Jaiswal & Nylandsted, 2015). Viral infection controlled by a calcium-dependent lipid-binding module in ALIX. This cell membrane provides a protective barrier around the cell and regulates which materials can pass in or out. These observations on PIP2 kinetics line up remarkably well with the accumulation of F-actin at the injury site, which begins around 30 seconds after injury and extends for several minutes (Godin, Vergen, Prakash, Pagano, & Hubmayr, 2011; Horn et al., 2017). Every cell has a fatty membrane that self-assembles when placed in water, then reassembles when a breach occurs. Unauthorized use of these marks is strictly prohibited. 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). Direct lipid modification of proteins, such as GTPases, provides another method to regulate protein localization and activity (Casey, 1995). Glycerol-3-phosphate is used to generate PA as well as PG through the intermediate phosphatidylglycerol phosphate (PGP). Shear stress on the plasma membrane also results in the dissociation of the negative regulator RhoGDI and its binding partner Rho (Shao et al., 2018). Gauthier NC, Masters TA, & Sheetz MP (2012). HHS Vulnerability Disclosure, Help Epub 2015 Oct 19. Among these lipids, PC is the most abundant in the plasma membrane and is formed by adding choline to the DAG backbone. Cell damage can be reversible or irreversible. FRET biosensor allows spatiotemporal observation of shear stress-induced polar RhoGDI activation. Shao S, Liao X, Xie F, Deng S, Liu X, Ristaniemi T, & Liu B (2018). Tran DT, Masedunskas A, Weigert R, & Ten Hagen KG (2015). Presence of LBPA at the plasma membrane through vesicle fusion could allow for ALIX recruitment and ESCRT assembly (Bissig et al., 2013); however, the presence of LBPA at membrane wound sites has not been directly observed. GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and skeletal muscle pathology in dystrophin-deficient mice. Stem cells in animal models of regeneration. 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). In response to an injury, a sudden change in hydrostatic pressure and local disassembly of the cortical cytoskeleton causes a rapid drop in membrane tension (Jaiswal et al., 2014; Miyake, McNeil, Suzuki, Tsunoda, & Sugai, 2001; Togo et al., 2000). It must repair itself, first by stopping the loss of cytoplasm, and then regenerate by rebuilding structures that were damaged or lost. Cell membrane repair repurposes mechanisms from various cellular functions, including vesicle trafficking, exocytosis, and endocytosis, to mend the broken membrane. However, shear force on the membrane increases the kinetic energy required for lipid mixing (i.e. A different model for plasma membrane repair began to emerge when mammalian cells injured mechanically or by SLO pores were found to undergo massive endocytosis, after Ca 2+ -triggered exocytosis of lysosomes ( Figure 1 C). Additional structural changes the plasma membrane must adopt for repair include molding the shape of the membrane to limit wound expansion as well as pulling in the membrane edges to close the wound. While reassembly of the cortical cytoskeleton in the minutes following injury is known to restore membrane tension (described in Section 3.3), membrane remodeling also contributes to increasing tension. Damage control: cellular mechanisms of plasma membrane repair. Very large plasma membrane disruptions (micron diameter) require membrane patching. Zhang KS, Blauch LR, Huang W, Marshall WF, Tang SKY. 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. Exocytic fusion reduces membrane tension, and vesicle-vesicle fusion events provide a patch as a replacement for the membrane barrier missing at the disruption site. The https:// ensures that you are connecting to the Curr Biol. Newer pharmacological approaches for antioxidant neuroprotection in traumatic brain injury. Copolymers such as poloxamer 188 avoid this potential issue by only stabilizing the plasma membrane once lipid packing density is sufficiently reduced, such as after an injury. Scheffer LL, Sreetama SC, Sharma N, Medikayala S, Brown KJ, Defour A, & Jaiswal JK (2014). Using these dating methods, it was inferred that fat cells (adipocytes) replace at a rate of 86% per year (BNID 103455). Definition. Mechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells, Long-term Potentiation of Wound-induced Exocytosis and Plasma Membrane Repair Is Dependant on cAMP-response Element-mediated Transcription via a Protein Kinase C-and p38 MAPK-dependent Pathway. 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). Role of LBPA and Alix in multivesicular liposome formation and endosome organization, Rac1 nanoscale organization on the plasma membrane is driven by lipid binding specificity encoded in the membrane anchor. National Library of Medicine Plasma membrane lipids containing the alkanoamine sphingosine are called sphingolipids. Necrosis is a progressive failure of essential metabolic and structural cell components usually in the cytoplasm. Membrane stabilization by modified steroid offers a potential therapy for muscular dystrophy due to dysferlin deficit, Transverse distribution of plasma membrane bilayer cholesterol: Picking sides. Rapid Changes to Endomembrane System of Infected Root Nodule Cells to Adapt to Unusual Lifestyle. 2012 Sep-Oct;52(3-4):191-5. doi: 10.1016/j.ceca.2012.06.003. Disruption of the cell plasma membrane is a commonplace occurrence in many mechanically challenging, biological environments. cell, in biology, the basic membrane-bound unit that contains the fundamental molecules of life and of which all living things are composed. The structural role of lipids may extend into the signaling role, which can then impact back on the structural characteristics of the repairing membrane by changing the composition or distribution of individual lipids. The mystery of membrane organization: composition, regulation and roles of lipid rafts. The https:// ensures that you are connecting to the 2021 Sep 29;9:753625. doi: 10.3389/fcell.2021.753625. The site is secure. However, lipid signaling also helps to coordinate downstream repair pathways that result in the membrane trafficking and cytoskeletal reorganization required for repair. Intriguingly, PA preferentially binds the Rho family member Rac1, resulting in nanocluster formation (Maxwell et al., 2018). The MG53 binding protein PTRF (cavin-1) binds cholesterol in response to membrane injury (Zhu et al., 2012). National Library of Medicine MG53 nucleates assembly of cell membrane repair machinery. Togo T, Krasieva TB, & Steinhardt RA (2000). Plasma membrane repair in health and disease. This remodeling is likely provided by processes described previously: membrane endocytosis (Section 3.1) and membrane shedding (Section 4.1). official website and that any information you provide is encrypted These lipids also exist at the boundary of lipid-ordered domains, such as lipid rafts, indicating that GTPases are targeted to these regions where protein accumulation at the membrane is common (Moissoglu et al., 2014), increasing their relative signaling capacity. Blauch LR, Gai Y, Khor JW, Sood P, Marshall WF, Tang SKY. 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. Int J Mol Sci. Epub 2008 Mar 3. The lipids in the membrane control the function of the membrane - keeping some products inside and some outside. Sood P, Lin A, Yan C, McGillivary R, Diaz U, Makushok T, Nadkarni AV, Tang SKY, Marshall WF. Interestingly, several methods for PIP2 micro-domain formation may allow for this to occur after plasma membrane injury. This results in the replacement of half of the body's adipocytes in 8 years. Copyright 2015 the American Physiological Society. These mediators promote wound resolution by acting upon the immune and endothelial cells and help to control the duration and nature of the immune and phagocytic cell infiltration at the injury site (Serhan, 2014).
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