20 min listen
Rab7 dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis
Rab7 dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis
ratings:
Length:
20 minutes
Released:
Feb 13, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.02.13.528320v1?rss=1
Authors: Gaur, P., Rajendran, Y., Srivastava, B., Markandey, M., Yoskovitz, V.-R., Mohapatra, G., Suhail, A., Choudhary, S., Tyagi, S., Yadav, S. C., Pandey, A. K., Merbl, Y., Bajaj, A., Ahuja, V., Srikanth, C.
Abstract:
Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier coupled with microbial dysbiosis has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease Chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7 dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2023.02.13.528320v1?rss=1
Authors: Gaur, P., Rajendran, Y., Srivastava, B., Markandey, M., Yoskovitz, V.-R., Mohapatra, G., Suhail, A., Choudhary, S., Tyagi, S., Yadav, S. C., Pandey, A. K., Merbl, Y., Bajaj, A., Ahuja, V., Srikanth, C.
Abstract:
Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier coupled with microbial dysbiosis has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease Chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7 dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Feb 13, 2023
Format:
Podcast episode
Titles in the series (100)
Endosomal removal and disposal of dysfunctional, immunostimulatory mitochondrial DNA by PaperPlayer biorxiv cell biology