scholarly journals Autophagy suppression by TORC1 maintains epithelial plasma membrane integrity and inhibits syncytium formation

2021 ◽  
Author(s):  
Parisa Kakanj ◽  
Sourabh Bhide ◽  
Bernard Moussian ◽  
Maria Leptin
Keyword(s):  
Wound Healing ◽  
Plasma Membrane ◽  
Stress Responses ◽  
Membrane Integrity ◽  
Syncytium Formation ◽  
Degradation Process ◽  
Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Epithelial Wound Healing ◽  
Membrane Isolation

Epithelial wound healing in Drosophila involves the formation of multinucleate cells surrounding the wound. We show that autophagy, a cellular degradation process often deployed in stress responses, is required for the formation of a multinucleated syncytium during wound healing. In addition, uncontrolled autophagy in the unwounded epidermis leads to the degradation of endo-membranes and the lateral plasma membrane, while the apical and basal membranes and the epithelial barrier function remain intact. Proper functioning of TORC1 is needed to prevent autophagy from destroying the larval epidermis, which depends on membrane isolation and phagophore expansion, but does not require the fusion of autophagosomes to lysosomes. Our findings reveal a function for TORC1-mediated regulation of autophagy in maintaining membrane integrity and homeostasis in the epidermis and during wound healing. Finally, autophagy can counteract experimentally induced nuclear defects resembling laminopathies.

scholarly journals Angulin-1 seals tricellular contacts independently of tricellulin and claudins

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Taichi Sugawara ◽  
Kyoko Furuse ◽  
Tetsuhisa Otani ◽  
Tomohiko Wakayama ◽  
Mikio Furuse
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Genome Editing ◽  
Tight Junctions ◽  
Barrier Function ◽  
Intercellular Space ◽  
Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
C Terminus ◽  
Membrane Contact

Tricellular tight junctions (tTJs) are specialized tight junctions (TJs) that seal the intercellular space at tricellular contacts (TCs), where the vertices of three epithelial cells meet. Tricellulin and angulin family membrane proteins are known constituents of tTJs, but the molecular mechanism of tTJ formation remains elusive. Here, we investigated the roles of angulin-1 and tricellulin in tTJ formation in MDCK II cells by genome editing. Angulin-1–deficient cells lost the plasma membrane contact at TCs with impaired epithelial barrier function. The C terminus of angulin-1 bound to the TJ scaffold protein ZO-1, and disruption of their interaction influenced the localization of claudins at TCs, but not the tricellular sealing. Strikingly, the plasma membrane contact at TCs was formed in tricellulin- or claudin-deficient cells. These findings demonstrate that angulin-1 is responsible for the plasma membrane seal at TCs independently of tricellulin and claudins.

scholarly journals Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin

2020 ◽  
Vol 117 (21) ◽  
pp. 11648-11657 ◽  
Author(s):  
Ruth X. Wang ◽  
J. Scott Lee ◽  
Eric L. Campbell ◽  
Sean P. Colgan
Keyword(s):  
Wound Healing ◽  
Barrier Function ◽  
Critical Role ◽  
Actin Binding ◽  
Mucosal Inflammation ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Intestinal Homeostasis ◽  
Epithelial Barrier Function

The intestinal mucosa exists in dynamic balance with trillions of luminal microbes. Disruption of the intestinal epithelial barrier, commonly observed in mucosal inflammation and diseases such as inflammatory bowel diseases (IBDs), is often associated with dysbiosis, particularly decreases in species producing short-chain fatty acids (SCFAs), such as butyrate. It remains unclear to what extent microbiota-derived factors contribute to the overall maintenance of intestinal homeostasis. Initial studies revealed that butyrate selectively promotes epithelial barrier function and wound healing. We aimed to define the specific mechanism(s) through which butyrate contributes to these epithelial responses. Guided by an unbiased profiling approach, we identified the dominant regulation of the actin-binding protein synaptopodin (SYNPO). Extensions of this work revealed a role for SYNPO in intestinal epithelial barrier function and wound healing. SYNPO was localized to the intestinal epithelial tight junction and within F-actin stress fibers where it is critical for barrier integrity and cell motility. Butyrate, but not other SCFAs, induced SYNPO in epithelial cell lines and murine colonic enteroids through mechanisms possibly involving histone deacetylase inhibition. Moreover, depletion of the microbiota abrogated expression of SYNPO in the mouse colon, which was rescued with butyrate repletion. Studies inSynpo-deficient mice demonstrated exacerbated disease susceptibility and increased intestinal permeability in a dextran sulfate sodium colitis model. These findings establish a critical role for the microbiota and their products, specifically butyrate, in the regulated expression of SYNPO for intestinal homeostasis and reveal a direct mechanistic link between microbiota-derived butyrate and barrier restoration.

scholarly journals Angulin-1 seals tricellular contacts independently of tricellulin and claudins

2020 ◽  
Author(s):  
Taichi Sugawara ◽  
Kyoko Furuse ◽  
Tetsuhisa Otani ◽  
Mikio Furuse
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Genome Editing ◽  
Tight Junctions ◽  
Molecular Mechanism ◽  
Barrier Function ◽  
Intercellular Space ◽  
Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Membrane Contact

AbstractTricellular tight junctions (tTJs) are specialized tight junctions (TJs) that seal the intercellular space at tricellular contacts (TCs), where the vertices of three epithelial cells meet. Tricellulin and angulin family membrane proteins are known constituents of tTJs, but the molecular mechanism of tTJ formation remains elusive. Here, we investigated the roles of angulin-1 and tricellulin in tTJ formation in MDCK II cells by genome editing. Angulin-1-deficient cells lost the plasma membrane contact at TCs with impaired epithelial barrier function. The COOH-terminus of angulin-1 bound to the TJ scaffold protein ZO-1 and disruption of their interaction influenced the localization of claudins at TCs, but not the tricellular sealing. Strikingly, the plasma membrane contact at TCs was formed in tricellulin- or claudin-deficient cells. These findings demonstrate that angulin-1 is responsible for the plasma membrane seal at TCs independently of tricellulin and claudins.

Comparision of DNA fragmentantion and plasma membrane integrity between chilled and frozen semen of bulls

2014 ◽  
Author(s):  
Mello Papa Patricia de ◽  
Carlos Ramires Neto ◽  
Priscilla Nascimento Guasti ◽  
Rosiara Rosaria Dias Maziero ◽  
Yame F R Sancler-Silva ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Integrity ◽  
Plasma Membrane Integrity ◽  
Frozen Semen
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