scholarly journals Endoplasmic reticulum maintains ion homeostasis required for plasma membrane repair

2021 ◽  
Vol 220 (5) ◽  
Author(s):  
Goutam Chandra ◽  
Sen Chandra Sreetama ◽  
Davi A.G. Mázala ◽  
Karine Charton ◽  
Jack H. VanderMeulen ◽  
...  

Of the many crucial functions of the ER, homeostasis of physiological calcium increase is critical for signaling. Plasma membrane (PM) injury causes a pathological calcium influx. Here, we show that the ER helps clear this surge in cytoplasmic calcium through an ER-resident calcium pump, SERCA, and a calcium-activated ion channel, Anoctamin 5 (ANO5). SERCA imports calcium into the ER, and ANO5 supports this by maintaining electroneutrality of the ER lumen through anion import. Preventing either of these transporter activities causes cytosolic calcium overload and disrupts PM repair (PMR). ANO5 deficit in limb girdle muscular dystrophy 2L (LGMD2L) patient cells compromises their cytosolic and ER calcium homeostasis. By generating a mouse model of LGMD2L, we find that PM injury causes cytosolic calcium overload and compromises the ability of ANO5-deficient myofibers to repair. Addressing calcium overload in ANO5-deficient myofibers enables them to repair, supporting the requirement of the ER in calcium homeostasis in injured cells and facilitating PMR.

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Adam Horn ◽  
Shreya Raavicharla ◽  
Sonna Shah ◽  
Dan Cox ◽  
Jyoti K. Jaiswal

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.


2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Goutam Chandra ◽  
Aurelia Defour ◽  
Kamel Mamchoui ◽  
Kalpana Pandey ◽  
Soumya Mishra ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Catarina Dias ◽  
Jesper Nylandsted

AbstractMaintenance of plasma membrane integrity is essential for normal cell viability and function. Thus, robust membrane repair mechanisms have evolved to counteract the eminent threat of a torn plasma membrane. Different repair mechanisms and the bio-physical parameters required for efficient repair are now emerging from different research groups. However, less is known about when these mechanisms come into play. This review focuses on the existence of membrane disruptions and repair mechanisms in both physiological and pathological conditions, and across multiple cell types, albeit to different degrees. Fundamentally, irrespective of the source of membrane disruption, aberrant calcium influx is the common stimulus that activates the membrane repair response. Inadequate repair responses can tip the balance between physiology and pathology, highlighting the significance of plasma membrane integrity. For example, an over-activated repair response can promote cancer invasion, while the inability to efficiently repair membrane can drive neurodegeneration and muscular dystrophies. The interdisciplinary view explored here emphasises the widespread potential of targeting plasma membrane repair mechanisms for therapeutic purposes.


2016 ◽  
Vol 213 (6) ◽  
pp. 613-615 ◽  
Author(s):  
Camilla Raiborg ◽  
Harald Stenmark

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.


2011 ◽  
Vol 287 (3) ◽  
pp. 1823-1836 ◽  
Author(s):  
Parini Mankad ◽  
Andrew James ◽  
Ajith K. Siriwardena ◽  
Austin C. Elliott ◽  
Jason I. E. Bruce

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stine Lauritzen Sønder ◽  
Theresa Louise Boye ◽  
Regine Tölle ◽  
Jörn Dengjel ◽  
Kenji Maeda ◽  
...  

2011 ◽  
Vol 81 (6) ◽  
pp. 703-712 ◽  
Author(s):  
Annette Draeger ◽  
Katia Monastyrskaya ◽  
Eduard B. Babiychuk

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