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Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis

In early blood vessel development, trafficking programs, such as those using Rab GTPases, are tasked with delivering vesicular cargo with high spatiotemporal accuracy. However, the function of many Rab trafficking proteins remain ill-defined in endothelial tissue; therefore, their relevance to blood...

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Autores principales: Francis, Caitlin R., Kincross, Hayle, Kushner, Erich J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458672/
https://www.ncbi.nlm.nih.gov/pubmed/36075898
http://dx.doi.org/10.1038/s41467-022-32853-5
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author Francis, Caitlin R.
Kincross, Hayle
Kushner, Erich J.
author_facet Francis, Caitlin R.
Kincross, Hayle
Kushner, Erich J.
author_sort Francis, Caitlin R.
collection PubMed
description In early blood vessel development, trafficking programs, such as those using Rab GTPases, are tasked with delivering vesicular cargo with high spatiotemporal accuracy. However, the function of many Rab trafficking proteins remain ill-defined in endothelial tissue; therefore, their relevance to blood vessel development is unknown. Rab35 has been shown to play an enigmatic role in cellular behaviors which differs greatly between tissue-type and organism. Importantly, Rab35 has never been characterized for its potential contribution in sprouting angiogenesis; thus, our goal was to map Rab35’s primary function in angiogenesis. Our results demonstrate that Rab35 is critical for sprout formation; in its absence, apicobasal polarity is entirely lost in vitro and in vivo. To determine mechanism, we systematically explored established Rab35 effectors and show that none are operative in endothelial cells. However, we find that Rab35 partners with DENNd1c, an evolutionarily divergent guanine exchange factor, to localize to actin. Here, Rab35 regulates actin polymerization through limiting Rac1 and RhoA activity, which is required to set up proper apicobasal polarity during sprout formation. Our findings establish that Rab35 is a potent brake of actin remodeling during blood vessel development.
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spelling pubmed-94586722022-09-10 Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis Francis, Caitlin R. Kincross, Hayle Kushner, Erich J. Nat Commun Article In early blood vessel development, trafficking programs, such as those using Rab GTPases, are tasked with delivering vesicular cargo with high spatiotemporal accuracy. However, the function of many Rab trafficking proteins remain ill-defined in endothelial tissue; therefore, their relevance to blood vessel development is unknown. Rab35 has been shown to play an enigmatic role in cellular behaviors which differs greatly between tissue-type and organism. Importantly, Rab35 has never been characterized for its potential contribution in sprouting angiogenesis; thus, our goal was to map Rab35’s primary function in angiogenesis. Our results demonstrate that Rab35 is critical for sprout formation; in its absence, apicobasal polarity is entirely lost in vitro and in vivo. To determine mechanism, we systematically explored established Rab35 effectors and show that none are operative in endothelial cells. However, we find that Rab35 partners with DENNd1c, an evolutionarily divergent guanine exchange factor, to localize to actin. Here, Rab35 regulates actin polymerization through limiting Rac1 and RhoA activity, which is required to set up proper apicobasal polarity during sprout formation. Our findings establish that Rab35 is a potent brake of actin remodeling during blood vessel development. Nature Publishing Group UK 2022-09-08 /pmc/articles/PMC9458672/ /pubmed/36075898 http://dx.doi.org/10.1038/s41467-022-32853-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Francis, Caitlin R.
Kincross, Hayle
Kushner, Erich J.
Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
title Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
title_full Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
title_fullStr Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
title_full_unstemmed Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
title_short Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
title_sort rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458672/
https://www.ncbi.nlm.nih.gov/pubmed/36075898
http://dx.doi.org/10.1038/s41467-022-32853-5
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