scholarly journals Plasma Membrane Repair: A Central Process for Maintaining Cellular Homeostasis

Physiology ◽  
2015 ◽  
Vol 30 (6) ◽  
pp. 438-448 ◽  
Author(s):  
Alisa D. Blazek ◽  
Brian J. Paleo ◽  
Noah Weisleder
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Cell Membrane ◽  
Cellular Response ◽  
Cellular Functions ◽  
Membrane Repair ◽  
Central Process ◽  
Plasma Membrane Repair ◽  
Molecular Machinery ◽  
Membrane Resealing

Plasma membrane repair is a conserved cellular response mediating active resealing of membrane disruptions to maintain homeostasis and prevent cell death and progression of multiple diseases. Cell membrane repair repurposes mechanisms from various cellular functions, including vesicle trafficking, exocytosis, and endocytosis, to mend the broken membrane. Recent studies increased our understanding of membrane repair by establishing the molecular machinery contributing to membrane resealing. Here, we review some of the key proteins linked to cell membrane repair.

scholarly journals Rab11 is required for lysosome exocytosis through the interaction with Rab3a, Sec15 and GRAB

2021 ◽  
Author(s):  
Cristina Escrevente ◽  
Liliana Bento-Lopes ◽  
José S. Ramalho ◽  
Duarte C. Barral
Keyword(s):  
Plasma Membrane ◽  
Cell Periphery ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Cellular Functions ◽  
Membrane Repair ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Plasma Membrane Repair ◽  
Molecular Machinery

Lysosomes are dynamic organelles, capable of undergoing exocytosis. This process is crucial for several cellular functions, namely plasma membrane repair. Nevertheless, the molecular machinery involved in this process is poorly understood. Here, we identify Rab11a and Rab11b as regulators of calcium-induced lysosome exocytosis. Interestingly, Rab11-positive vesicles transiently interact with lysosomes at the cell periphery, indicating that this interaction is required for the last steps of lysosome exocytosis. Additionally, we found that the silencing of the exocyst subunit Sec15, a Rab11 effector, impairs lysosome exocytosis, suggesting that Sec15 acts together with Rab11 in the regulation of lysosome exocytosis. Furthermore, we show that Rab11 binds the guanine nucleotide exchange factor for Rab3a (GRAB) and also Rab3a, which we described previously as a regulator of the positioning and exocytosis of lysosomes. Thus, our study identifies new players required for lysosome exocytosis and suggest the existence of a Rab11-Rab3a cascade involved in this process.

scholarly journals A novel Rab11-Rab3a cascade required for lysosome exocytosis

2021 ◽  
Author(s):  
Cristina Escrevente ◽  
Liliana Bento-Lopes ◽  
José S Ramalho ◽  
Duarte C Barral
Keyword(s):  
Plasma Membrane ◽  
Cell Periphery ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Cellular Functions ◽  
Membrane Repair ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Plasma Membrane Repair ◽  
Molecular Machinery

AbstractLysosomes are dynamic organelles, capable of undergoing exocytosis. This process is crucial for several cellular functions, namely plasma membrane repair. Nevertheless, the molecular machinery involved in this process is poorly understood.Here, we identify Rab11a and Rab11b as regulators of calcium-induced lysosome exocytosis. Interestingly, Rab11-positive vesicles transiently interact with lysosomes at the cell periphery, indicating that this interaction is required for the last steps of lysosome exocytosis. Additionally, we found that the silencing of the exocyst subunit Sec15, a Rab11 effector, impairs lysosome exocytosis independently of the exocyst complex, suggesting that Sec15 acts together with Rab11 in the regulation of lysosome exocytosis. Furthermore, we show that Rab11 binds the guanine nucleotide exchange factor for Rab3a (GRAB) and also Rab3a, which we described previously as a regulator of the positioning and exocytosis of lysosomes.Thus, our studies suggest that Rab11-positive vesicles transport GRAB to activate Rab3a on lysosomes, establishing a Rab11-Rab3 cascade that is essential for lysosome exocytosis.

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

2016 ◽  
Vol 213 (6) ◽  
pp. 705-718 ◽  
Author(s):  
Alexis R. Demonbreun ◽  
Mattia Quattrocelli ◽  
David Y. Barefield ◽  
Madison V. Allen ◽  
Kaitlin E. Swanson ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Muscle Fibers ◽  
Membrane Repair ◽  
Muscle Plasma Membrane ◽  
Shoulder Region ◽  
Plasma Membrane Repair ◽  
Molecular Machinery ◽  
Membrane Resealing ◽  
Efficient Recovery ◽  
High Resolution Microscopy

Disruption of the plasma membrane often accompanies cellular injury, and in muscle, plasma membrane resealing is essential for efficient recovery from injury. Muscle contraction, especially of lengthened muscle, disrupts the sarcolemma. To define the molecular machinery that directs repair, we applied laser wounding to live mammalian myofibers and assessed translocation of fluorescently tagged proteins using high-resolution microscopy. Within seconds of membrane disruption, annexins A1, A2, A5, and A6 formed a tight repair “cap.” Actin was recruited to the site of damage, and annexin A6 cap formation was both actin dependent and Ca2+ regulated. Repair proteins, including dysferlin, EHD1, EHD2, MG53, and BIN1, localized adjacent to the repair cap in a “shoulder” region enriched with phosphatidlyserine. Dye influx into muscle fibers lacking both dysferlin and the related protein myoferlin was substantially greater than control or individual null muscle fibers, underscoring the importance of shoulder-localized proteins. These data define the cap and shoulder as subdomains within the repair complex accumulating distinct and nonoverlapping components.

scholarly journals Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair

2010 ◽  
Vol 189 (6) ◽  
pp. 1027-1038 ◽  
Author(s):  
Christina Tam ◽  
Vincent Idone ◽  
Cecilia Devlin ◽  
Maria Cecilia Fernandes ◽  
Andrew Flannery ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lysosomal Enzyme ◽  
Membrane Integrity ◽  
Acid Sphingomyelinase ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Cellular Survival ◽  
Plasma Membrane Repair ◽  
Membrane Resealing ◽  
Niemann Pick

Rapid plasma membrane resealing is essential for cellular survival. Earlier studies showed that plasma membrane repair requires Ca2+-dependent exocytosis of lysosomes and a rapid form of endocytosis that removes membrane lesions. However, the functional relationship between lysosomal exocytosis and the rapid endocytosis that follows membrane injury is unknown. In this study, we show that the lysosomal enzyme acid sphingomyelinase (ASM) is released extracellularly when cells are wounded in the presence of Ca2+. ASM-deficient cells, including human cells from Niemann-Pick type A (NPA) patients, undergo lysosomal exocytosis after wounding but are defective in injury-dependent endocytosis and plasma membrane repair. Exogenously added recombinant human ASM restores endocytosis and resealing in ASM-depleted cells, suggesting that conversion of plasma membrane sphingomyelin to ceramide by this lysosomal enzyme promotes lesion internalization. These findings reveal a molecular mechanism for restoration of plasma membrane integrity through exocytosis of lysosomes and identify defective plasma membrane repair as a possible component of the severe pathology observed in NPA patients.

scholarly journals A Rab3a-dependent complex essential for lysosome positioning and plasma membrane repair

2016 ◽  
Vol 213 (6) ◽  
pp. 631-640 ◽  
Author(s):  
Marisa Encarnação ◽  
Lília Espada ◽  
Cristina Escrevente ◽  
Denisa Mateus ◽  
José Ramalho ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Cell Periphery ◽  
Perinuclear Region ◽  
Nonmuscle Myosin ◽  
Membrane Repair ◽  
Rab Family ◽  
Plasma Membrane Repair ◽  
Molecular Machinery

Lysosome exocytosis plays a major role in resealing plasma membrane (PM) disruptions. This process involves two sequential steps. First, lysosomes are recruited to the periphery of the cell and then fuse with the damaged PM. However, the trafficking molecular machinery involved in lysosome exocytosis and PM repair (PMR) is poorly understood. We performed a systematic screen of the human Rab family to identify Rabs required for lysosome exocytosis and PMR. Rab3a, which partially localizes to peripheral lysosomes, was one of the most robust hits. Silencing of Rab3a or its effector, synaptotagmin-like protein 4a (Slp4-a), leads to the collapse of lysosomes to the perinuclear region and inhibition of PMR. Importantly, we have also identified a new Rab3 effector, nonmuscle myosin heavy chain IIA, as part of the complex formed by Rab3a and Slp4-a that is responsible for lysosome positioning at the cell periphery and lysosome exocytosis.

scholarly journals Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice

2003 ◽  
Vol 162 (4) ◽  
pp. 543-549 ◽  
Author(s):  
Sabyasachi Chakrabarti ◽  
Koichi S. Kobayashi ◽  
Richard A. Flavell ◽  
Carolyn B. Marks ◽  
Katsuya Miyake ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Inflammatory Myopathy ◽  
Response Characteristic ◽  
Membrane Repair ◽  
Progressive Muscle Weakness ◽  
Autoimmune Myositis ◽  
Mouse Tissues ◽  
Plasma Membrane Repair ◽  
Membrane Resealing ◽  
Deficient Mice

Members of the synaptotagmin family have been proposed to function as Ca2+ sensors in membrane fusion. Syt VII is a ubiquitously expressed synaptotagmin previously implicated in plasma membrane repair and Trypanosoma cruzi invasion, events which are mediated by the Ca2+-regulated exocytosis of lysosomes. Here, we show that embryonic fibroblasts from Syt VII–deficient mice are less susceptible to trypanosome invasion, and defective in lysosomal exocytosis and resealing after wounding. Examination of mutant mouse tissues revealed extensive fibrosis in the skin and skeletal muscle. Inflammatory myopathy, with muscle fiber invasion by leukocytes and endomysial collagen deposition, was associated with elevated creatine kinase release and progressive muscle weakness. Interestingly, similar to what is observed in human polymyositis/dermatomyositis, the mice developed a strong antinuclear antibody response, characteristic of autoimmune disorders. Thus, defective plasma membrane repair in tissues under mechanical stress may favor the development of inflammatory autoimmune disease.

The mechanism of cell membrane repair

Zygote ◽  
1999 ◽  
Vol 8 (S1) ◽  
pp. S31-S32 ◽  
Author(s):  
Tatsuru Togo ◽  
Janet M. Alderton ◽  
Richard A. Steinhardt
Keyword(s):  
Plasma Membrane ◽  
Sea Urchin ◽  
Plasma Membranes ◽  
Membrane Repair ◽  
Sea Urchin Egg ◽  
Calmodulin Kinase ◽  
Intracellular Ca ◽  
Plasma Membrane Repair ◽  
Botulinum Neurotoxins ◽  
Membrane Resealing

Disruption of plasma membranes is a widespread, common and normal event that occurs in many mechanically challenged tissues (McNeil & Steinhardt, 1997). After injury to the plasma membrane, rapid resealing of the membrane occurs with little loss of intracellular contents.Analysis of plasma membrane repair in the sea urchin egg and early embryos revealed a new model of the mechanism for plasma membrane repair. Resealing of disrupted plasma membranes required external Ca2+ that could be antagonised by Mg2+. Block of Ca2+/calmodulin kinase II, which regulates exocytotic vesicle availability at synapses (Llinás et al., 1991), inhibited membrane resealing. Resealing was also inhibited by botulinum neurotoxins A, B, C1, and tetanus toxin, which disrupt SNARE vesicle docking/fusion proteins. Confocal microscopic observations of exocytotic events in sea urchin eggs and embryos during membrane resealing showed that inhibition of kinesin or myosin motor activity, which are believed to be required for vesicle transport (Goodson et al., 1997), also inhibited membrane resealing and delivery of vesicles to sites of membrane disruption. This pattern of inhibition indicates that membrane repair of micrometre-sized lesions requires vesicle delivery, docking and fusion, similar to the exocytosis of neurotransmitter (Steinhardt et al., 1994; Bi et al., 1995, 1997).The mechanism of resealing in eggs and embyros was found to be a general property of all cells (Steinhardt et al., 1994; Togo et al., 1999). It is now known that elevated intracellular Ca2+ triggers exocytosis in various types of cells (Dan & Poo, 1992; Coorssen et al., 1996), and that endosomal compartments such as lysosomes can behave as Ca2+-regulated exocytotic vesicles (Rodríguez et al., 1997).

scholarly journals Plasma membrane repairs by small GTPase Rab3a

2016 ◽  
Vol 213 (6) ◽  
pp. 613-615 ◽  
Author(s):  
Camilla Raiborg ◽  
Harald Stenmark
Keyword(s):  
Plasma Membrane ◽  
Small Gtpase ◽  
Membrane Repair ◽  
Cell Biol ◽  
Plasma Membrane Repair

Lysosomes fuse with the plasma membrane to help repair membrane lesions, but how they are positioned close to these lesions is not fully understood. Now, Encarnação et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201511093) demonstrate that the lysosomal GTPase Rab3a and its effectors orchestrate lysosome positioning and plasma membrane repair.

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