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TBC1D15 potentiates lysosomal regeneration from damaged membranes
TBC1D15 potentiates lysosomal regeneration from damaged membranes
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Length:
20 minutes
Released:
Dec 15, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.12.14.520480v1?rss=1
Authors: Bhattacharya, A., Mukherjee, R., Kuncha, S. K., Brunstein, M., Rathore, R., Junek, S., Munch, C., Dikic, I.
Abstract:
Acute lysosomal membrane damage reduces the cellular population of functional lysosomes. However, these damaged lysosomes have a remarkable recovery potential independent of lysosomal biogenesis and remain unaffected in TFEB/TFE3-depleted cells. We combined proximity labelling based proteomics, biochemistry and high resolution microscopy to unravel a new lysosomal membrane regeneration pathway which is dependent on ATG8, lysosomal membrane protein LIMP2, the Rab7 GAP TBC1D15, and proteins required for autophagic lysosomal reformation (ALR) including Dynamin2, Kinesin5B and Clathrin. Upon lysosomal damage, LIMP2 act as a lysophagy receptor to bind ATG8, which in turn recruits TBC1D15 to damaged membranes. TBC1D15 hydrolyses Rab7-GTP to segregate the damaged lysosomal mass and provides a scaffold to assemble and stabilize the ALR machinery, potentiating the formation of lysosomal tubules and subsequent Dynamin2-dependent scission. TBC1D15-mediated lysosome regeneration was also observed in a cell culture model of oxalate nephropathy.
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http://biorxiv.org/cgi/content/short/2022.12.14.520480v1?rss=1
Authors: Bhattacharya, A., Mukherjee, R., Kuncha, S. K., Brunstein, M., Rathore, R., Junek, S., Munch, C., Dikic, I.
Abstract:
Acute lysosomal membrane damage reduces the cellular population of functional lysosomes. However, these damaged lysosomes have a remarkable recovery potential independent of lysosomal biogenesis and remain unaffected in TFEB/TFE3-depleted cells. We combined proximity labelling based proteomics, biochemistry and high resolution microscopy to unravel a new lysosomal membrane regeneration pathway which is dependent on ATG8, lysosomal membrane protein LIMP2, the Rab7 GAP TBC1D15, and proteins required for autophagic lysosomal reformation (ALR) including Dynamin2, Kinesin5B and Clathrin. Upon lysosomal damage, LIMP2 act as a lysophagy receptor to bind ATG8, which in turn recruits TBC1D15 to damaged membranes. TBC1D15 hydrolyses Rab7-GTP to segregate the damaged lysosomal mass and provides a scaffold to assemble and stabilize the ALR machinery, potentiating the formation of lysosomal tubules and subsequent Dynamin2-dependent scission. TBC1D15-mediated lysosome regeneration was also observed in a cell culture model of oxalate nephropathy.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Dec 15, 2022
Format:
Podcast episode
Titles in the series (100)
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