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A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells

Multiple Rabs are associated with secretory granules/vesicles, but how these GTPases are coordinated to promote regulated exocytosis is not well understood. In bladder umbrella cells a subapical pool of discoidal/fusiform-shaped vesicles (DFVs) undergoes Rab11a-dependent regulated exocytosis in resp...

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Autores principales: Khandelwal, Puneet, Prakasam, H. Sandeep, Clayton, Dennis R., Ruiz, Wily G., Gallo, Luciana I., van Roekel, Daniel, Lukianov, Stefan, Peränen, Johan, Goldenring, James R., Apodaca, Gerard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608489/
https://www.ncbi.nlm.nih.gov/pubmed/23389633
http://dx.doi.org/10.1091/mbc.E12-08-0568
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author Khandelwal, Puneet
Prakasam, H. Sandeep
Clayton, Dennis R.
Ruiz, Wily G.
Gallo, Luciana I.
van Roekel, Daniel
Lukianov, Stefan
Peränen, Johan
Goldenring, James R.
Apodaca, Gerard
author_facet Khandelwal, Puneet
Prakasam, H. Sandeep
Clayton, Dennis R.
Ruiz, Wily G.
Gallo, Luciana I.
van Roekel, Daniel
Lukianov, Stefan
Peränen, Johan
Goldenring, James R.
Apodaca, Gerard
author_sort Khandelwal, Puneet
collection PubMed
description Multiple Rabs are associated with secretory granules/vesicles, but how these GTPases are coordinated to promote regulated exocytosis is not well understood. In bladder umbrella cells a subapical pool of discoidal/fusiform-shaped vesicles (DFVs) undergoes Rab11a-dependent regulated exocytosis in response to bladder filling. We show that Rab11a-associated vesicles are enmeshed in an apical cytokeratin meshwork and that Rab11a likely acts upstream of Rab8a to promote exocytosis. Surprisingly, expression of Rabin8, a previously described Rab11a effector and guanine nucleotide exchange factor for Rab8, stimulates stretch-induced exocytosis in a manner that is independent of its catalytic activity. Additional studies demonstrate that the unconventional motor protein myosin5B motor (Myo5B) works in association with the Rab8a–Rab11a module to promote exocytosis, possibly by ensuring transit of DFVs through a subapical, cortical actin cytoskeleton before fusion. Our results indicate that Rab11a, Rab8a, and Myo5B function as part of a network to promote stretch-induced exocytosis, and we predict that similarly organized Rab networks will be common to other regulated secretory pathways.
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spelling pubmed-36084892013-06-16 A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells Khandelwal, Puneet Prakasam, H. Sandeep Clayton, Dennis R. Ruiz, Wily G. Gallo, Luciana I. van Roekel, Daniel Lukianov, Stefan Peränen, Johan Goldenring, James R. Apodaca, Gerard Mol Biol Cell Articles Multiple Rabs are associated with secretory granules/vesicles, but how these GTPases are coordinated to promote regulated exocytosis is not well understood. In bladder umbrella cells a subapical pool of discoidal/fusiform-shaped vesicles (DFVs) undergoes Rab11a-dependent regulated exocytosis in response to bladder filling. We show that Rab11a-associated vesicles are enmeshed in an apical cytokeratin meshwork and that Rab11a likely acts upstream of Rab8a to promote exocytosis. Surprisingly, expression of Rabin8, a previously described Rab11a effector and guanine nucleotide exchange factor for Rab8, stimulates stretch-induced exocytosis in a manner that is independent of its catalytic activity. Additional studies demonstrate that the unconventional motor protein myosin5B motor (Myo5B) works in association with the Rab8a–Rab11a module to promote exocytosis, possibly by ensuring transit of DFVs through a subapical, cortical actin cytoskeleton before fusion. Our results indicate that Rab11a, Rab8a, and Myo5B function as part of a network to promote stretch-induced exocytosis, and we predict that similarly organized Rab networks will be common to other regulated secretory pathways. The American Society for Cell Biology 2013-04-01 /pmc/articles/PMC3608489/ /pubmed/23389633 http://dx.doi.org/10.1091/mbc.E12-08-0568 Text en © 2013 Khandelwal et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Khandelwal, Puneet
Prakasam, H. Sandeep
Clayton, Dennis R.
Ruiz, Wily G.
Gallo, Luciana I.
van Roekel, Daniel
Lukianov, Stefan
Peränen, Johan
Goldenring, James R.
Apodaca, Gerard
A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells
title A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells
title_full A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells
title_fullStr A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells
title_full_unstemmed A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells
title_short A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells
title_sort rab11a-rab8a-myo5b network promotes stretch-regulated exocytosis in bladder umbrella cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608489/
https://www.ncbi.nlm.nih.gov/pubmed/23389633
http://dx.doi.org/10.1091/mbc.E12-08-0568
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