scholarly journals Annexin A2 Mediates Dysferlin Accumulation and Muscle Cell Membrane Repair

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1919 ◽  
Author(s):  
Daniel C. Bittel ◽  
Goutam Chandra ◽  
Laxmi M. S. Tirunagri ◽  
Arun B. Deora ◽  
Sushma Medikayala ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Membrane ◽  
Muscle Cell ◽  
Cytosolic Calcium ◽  
Annexin A2 ◽  
Mechanical Activity ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Cell Plasma ◽  
Muscle Cell Membrane

Muscle cell plasma membrane is frequently damaged by mechanical activity, and its repair requires the membrane protein dysferlin. We previously identified that, similar to dysferlin deficit, lack of annexin A2 (AnxA2) also impairs repair of skeletal myofibers. Here, we have studied the mechanism of AnxA2-mediated muscle cell membrane repair in cultured muscle cells. We find that injury-triggered increase in cytosolic calcium causes AnxA2 to bind dysferlin and accumulate on dysferlin-containing vesicles as well as with dysferlin at the site of membrane injury. AnxA2 accumulates on the injured plasma membrane in cholesterol-rich lipid microdomains and requires Src kinase activity and the presence of cholesterol. Lack of AnxA2 and its failure to translocate to the plasma membrane, both prevent calcium-triggered dysferlin translocation to the plasma membrane and compromise repair of the injured plasma membrane. Our studies identify that Anx2 senses calcium increase and injury-triggered change in plasma membrane cholesterol to facilitate dysferlin delivery and repair of the injured plasma membrane.

Electrical properties of smooth muscle cell membrane of opossum esophagus

1985 ◽  
Vol 248 (3) ◽  
pp. G342-G346 ◽  
Author(s):  
M. S. Kannan ◽  
L. P. Jager ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Electrical Properties ◽  
Cell Membrane ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Smooth Muscles ◽  
Mechanical Activity ◽  
Circular Smooth Muscle ◽  
Stimulation Of ◽  
Muscle Cell Membrane

The electrical properties of the circular smooth muscle layer from the North American opossum esophagus (body) were studied in vitro by microelectrode recording techniques, both at rest and during stimulation of intramural inhibitory nerves. All observations were made at 37 degrees C in an Abe-Tomita partitioned bath on muscle strips dissected 2 cm orad of the lower esophageal sphincter. At rest, the potential of the smooth muscle cell membrane was -49 +/- 4 mV (mean +/- SE); the length constant and the time constant were 2.0 +/- 0.6 mm and 120 +/- 16 ms, respectively. The inhibitory junction potential (IJP) elicited by stimulation of intramural nerves was followed by a "rebound" or "off" response, characterized by a membrane depolarization on which spikes were superimposed and concomitant mechanical activity of the preparation that usually caused dislocation of the recording microelectrode. The maximal IJP amplitude was 35 mV, and the response reversed at a membrane polarization to -90 mV, suggesting that the IJP was due to an increase of the permeability toward potassium ions. The invariability of the IJP latency at different distances from the stimulating electrodes (1.25-4 mm) suggests that the latency is largely due to diffusion of transmitter from nerve varicosities to postsynaptic receptor sites. Depending on the rate, prolonged stimulation caused fusion of IJP or a continuous hyperpolarization of the membrane. The hyperpolarization faded with time, but off responses were only observed after terminating stimulation. The passive electrical properties of the membrane are comparable with those of other gastrointestinal smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Novel autoantibodies against muscle-cell membrane proteins in patients with myositis

1996 ◽  
Vol 39 (11) ◽  
pp. 1860-1868 ◽  
Author(s):  
Bruno Stuhlmüller ◽  
Ricardo Jerez ◽  
Gert Hausdorf ◽  
Hans-R. Barthel ◽  
Michael Meurer ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Cell Membrane ◽  
Muscle Cell ◽  
Cell Membrane Proteins ◽  
Muscle Cell Membrane

scholarly journals Lipid raft–dependent plasma membrane repair interferes with the activation of B lymphocytes

2015 ◽  
Vol 211 (6) ◽  
pp. 1193-1205 ◽  
Author(s):  
Heather Miller ◽  
Thiago Castro-Gomes ◽  
Matthias Corrotte ◽  
Christina Tam ◽  
Timothy K. Maugel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
B Cell ◽  
B Lymphocytes ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Cell Activation ◽  
Dependent Manner ◽  
B Cell Activation ◽  
Membrane Repair ◽  
Membrane Injury

Cells rapidly repair plasma membrane (PM) damage by a process requiring Ca2+-dependent lysosome exocytosis. Acid sphingomyelinase (ASM) released from lysosomes induces endocytosis of injured membrane through caveolae, membrane invaginations from lipid rafts. How B lymphocytes, lacking any known form of caveolin, repair membrane injury is unknown. Here we show that B lymphocytes repair PM wounds in a Ca2+-dependent manner. Wounding induces lysosome exocytosis and endocytosis of dextran and the raft-binding cholera toxin subunit B (CTB). Resealing is reduced by ASM inhibitors and ASM deficiency and enhanced or restored by extracellular exposure to sphingomyelinase. B cell activation via B cell receptors (BCRs), a process requiring lipid rafts, interferes with PM repair. Conversely, wounding inhibits BCR signaling and internalization by disrupting BCR–lipid raft coclustering and by inducing the endocytosis of raft-bound CTB separately from BCR into tubular invaginations. Thus, PM repair and B cell activation interfere with one another because of competition for lipid rafts, revealing how frequent membrane injury and repair can impair B lymphocyte–mediated immune responses.

Ammonia movement and distribution after exercise across white muscle cell membranes in rainbow trout

1996 ◽  
Vol 271 (3) ◽  
pp. R738-R750 ◽  
Author(s):  
Y. Wang ◽  
G. J. Heigenhauser ◽  
C. M. Wood
Keyword(s):  
Membrane Potential ◽  
Cell Membrane ◽  
Intracellular Ph ◽  
Muscle Cell ◽  
Cell Membranes ◽  
White Muscle ◽  
Extracellular Ph ◽  
Posterior Portion ◽  
Arterial Inflow ◽  
Muscle Cell Membrane

Manipulations of pH and electrical gradients in a perfused preparation were used to analyze the factors controlling ammonia distribution and flux in trout white muscle after exercise. Trout were exercised to exhaustion, and then an isolated-perfused white muscle preparation with discrete arterial inflow and venous outflow was made from the posterior portion of the tail. The tail-trunks were perfused with low (7.4)-, medium (7.9)-, and high (8.4)-pH saline, achieved by varying HCO3- concentration ([HCO3-]) at constant Pco2. Intracellular and extracellular pH, ammonia, CO2, K+, Na+, and Cl- were measured. Muscle intracellular pH was not affected by changes in extracellular pH. Increasing extracellular pH caused a decrease in the transmembrane NH3 partial pressure (PNH3) gradient and a decrease in ammonia efflux. When extracellular K+ concentration was increased from 3.5 to 15 mM in the medium-pH group, a depolarization of the muscle cell membrane potential from -92 to -60 mV and a 0.1-unit depression in intracellular pH occurred. Ammonia efflux increased despite a marked reduction in the PNH3 gradient. Amiloride (10(-4) M) had no effect, indicating that Na+/H(+)-NH4+ exchange does not participate in ammonia transport in this system. A comparison of observed intracellular-to-extracellular ammonia distribution ratios with those modeled according to either pH or Nernst potential distributions supports a model in which ammonia distribution across white muscle cell membranes is affected by both pH and electrical gradients, indicating that the membranes are permeable to both NH3 and NH4+. Membrane potential, acting to retain high levels of NH4+ in the intracellular compartment, appears to have the dominant influence during the postexercise period. However, at rest, the pH gradient may be more important, resulting in much lower intracellular ammonia levels and distribution ratios. We speculate that the muscle cell membrane NH3-to-NH4+ permeability ratio in trout may change between the rest and postexercise condition.

scholarly journals Mitochondrial fragmentation enables localized signaling required for cell repair

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Adam Horn ◽  
Shreya Raavicharla ◽  
Sonna Shah ◽  
Dan Cox ◽  
Jyoti K. Jaiswal
Keyword(s):  
Plasma Membrane ◽  
Calcium Influx ◽  
Cell Damage ◽  
Mitochondrial Fission ◽  
Adaptor Protein ◽  
Mitochondrial Fragmentation ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Mitochondrial Signaling ◽  
Plasma Membrane Repair

Plasma membrane injury can cause lethal influx of calcium, but cells survive by mounting a polarized repair response targeted to the wound site. Mitochondrial signaling within seconds after injury enables this response. However, as mitochondria are distributed throughout the cell in an interconnected network, it is unclear how they generate a spatially restricted signal to repair the plasma membrane wound. Here we show that calcium influx and Drp1-mediated, rapid mitochondrial fission at the injury site help polarize the repair response. Fission of injury-proximal mitochondria allows for greater amplitude and duration of calcium increase in these mitochondria, allowing them to generate local redox signaling required for plasma membrane repair. Drp1 knockout cells and patient cells lacking the Drp1 adaptor protein MiD49 fail to undergo injury-triggered mitochondrial fission, preventing polarized mitochondrial calcium increase and plasma membrane repair. Although mitochondrial fission is considered to be an indicator of cell damage and death, our findings identify that mitochondrial fission generates localized signaling required for cell survival.

scholarly journals Loss of calpains-1 and -2 prevents repair of plasma membrane scrape injuries, but not small pores, and induces a severe muscular dystrophy

2020 ◽  
Vol 318 (6) ◽  
pp. C1226-C1237
Author(s):  
Ann-Katrin Piper ◽  
Reece A. Sophocleous ◽  
Samuel E. Ross ◽  
Frances J. Evesson ◽  
Omar Saleh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Muscular Dystrophy ◽  
Disease Genes ◽  
Spastic Paraplegia ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Streptolysin O ◽  
Calpain 2 ◽  
Cytoskeletal Networks

The ubiquitous calpains, calpain-1 and -2, play important roles in Ca2+-dependent membrane repair. Mechanically active tissues like skeletal muscle are particularly reliant on mechanisms to repair and remodel membrane injury, such as those caused by eccentric damage. We demonstrate that calpain-1 and -2 are master effectors of Ca2+-dependent repair of mechanical plasma membrane scrape injuries, although they are dispensable for repair/removal of small wounds caused by pore-forming agents. Using CRISPR gene-edited human embryonic kidney 293 (HEK293) cell lines, we established that loss of both calpains-1 and -2 ( CAPNS1−/−) virtually ablates Ca2+-dependent repair of mechanical scrape injuries but does not affect injury or recovery from perforation by streptolysin-O or saponin. In contrast, cells with targeted knockout of either calpain-1 ( CAPN1−/−) or -2 ( CAPN2−/−) show near-normal repair of mechanical injuries, inferring that both calpain-1 and calpain-2 are equally capable of conducting the cascade of proteolytic cleavage events to reseal a membrane injury, including that of the known membrane repair agent dysferlin. A severe muscular dystrophy in a murine model with skeletal muscle knockout of Capns1 highlights vital roles for calpain-1 and/or -2 for health and viability of skeletal muscles not compensated for by calpain-3 ( CAPN3). We propose that the dystrophic phenotype relates to loss of maintenance of plasma membrane/cytoskeletal networks by calpains-1 and -2 in response to directed and dysfunctional Ca2+-signaling, pathways hyperstimulated in the context of membrane injury. With CAPN1 variants associated with spastic paraplegia, a severe dystrophy observed with muscle-specific loss of calpain-1 and -2 activity identifies CAPN2 and CAPNS1 as plausible candidate neuromuscular disease genes.

A small synthetic molecule forms selective potassium channels to regulate cell membrane potential and blood vessel tone

2014 ◽  
Vol 12 (41) ◽  
pp. 8174-8179 ◽  
Author(s):  
Hui-Yan Zha ◽  
Bing Shen ◽  
Kwok-Hei Yau ◽  
Shing-To Li ◽  
Xiao-Qiang Yao ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Potassium Channels ◽  
Cell Membrane ◽  
Blood Vessel ◽  
Muscle Cell ◽  
Cell Membrane Potential ◽  
Vascular Muscle ◽  
Selective Channel ◽  
Synthetic Molecule ◽  
Muscle Cell Membrane

A molecule forms a K+-selective channel in the cell membrane to regulate vascular muscle cell membrane potential and blood vessel tone.

scholarly journals The UNC-112 Gene in Caenorhabditis elegansEncodes a Novel Component of Cell–Matrix Adhesion Structures Required for Integrin Localization in the Muscle Cell Membrane

2000 ◽  
Vol 150 (1) ◽  
pp. 253-264 ◽  
Author(s):  
Teresa M. Rogalski ◽  
Gregory P. Mullen ◽  
Mary M. Gilbert ◽  
Benjamin D. Williams ◽  
Donald G. Moerman
Keyword(s):  
Cell Membrane ◽  
Muscle Cell ◽  
Body Wall ◽  
Dense Body ◽  
The Body ◽  
Body Wall Muscle ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Cell Matrix Adhesion ◽  
Muscle Cell Membrane

Embryos homozygous for mutations in the unc-52, pat-2, pat-3, and unc-112 genes of C. elegans exhibit a similar Pat phenotype. Myosin and actin are not organized into sarcomeres in the body wall muscle cells of these mutants, and dense body and M-line components fail to assemble. The unc-52 (perlecan), pat-2 (α-integrin), and pat-3 (β-integrin) genes encode ECM or transmembrane proteins found at the cell–matrix adhesion sites of both dense bodies and M-lines. This study describes the identification of the unc-112 gene product, a novel, membrane-associated, intracellular protein that colocalizes with integrin at cell–matrix adhesion complexes. The 720–amino acid UNC-112 protein is homologous to Mig-2, a human protein of unknown function. These two proteins share a region of homology with talin and members of the FERM superfamily of proteins. We have determined that a functional UNC-112::GFP fusion protein colocalizes with PAT-3/β-integrin in both adult and embryonic body wall muscle. We also have determined that UNC-112 is required to organize PAT-3/β-integrin after it is integrated into the basal cell membrane, but is not required to organize UNC-52/perlecan in the basement membrane, nor for DEB-1/vinculin to localize with PAT-3/β-integrin. Furthermore, UNC-112 requires the presence of UNC-52/perlecan and PAT-3/β-integrin, but not DEB-1/vinculin to become localized to the muscle cell membrane.

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