Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis

Cell-cell junctions undergo constant remodeling, which is crucial for the control of vascular integrity. Indeed, transport of junctional components such as cadherins is understood in increasing depth. However, little is known about the respective pathways regulating localization of nectin at cell-ce...

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Autores principales:	Pasquale Cervero, Kirsten Vrenken, Matthias Klose, Kerstin Rehm, Stefan Linder
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Adherens junctions Drebrin Endocytosis Nectin RabGTPases Rab5a Cytology QH573-671
Acceso en línea:	https://doaj.org/article/88195ab62a2d4630bda82262a65d2faa
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spelling	oai:doaj.org-article:88195ab62a2d4630bda82262a65d2faa2021-11-26T04:23:44ZNectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis0171-933510.1016/j.ejcb.2021.151184https://doaj.org/article/88195ab62a2d4630bda82262a65d2faa2021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0171933521000352https://doaj.org/toc/0171-9335Cell-cell junctions undergo constant remodeling, which is crucial for the control of vascular integrity. Indeed, transport of junctional components such as cadherins is understood in increasing depth. However, little is known about the respective pathways regulating localization of nectin at cell-cell junctions. Here, we performed an siRNA-based screen of vesicle regulators of the RabGTPase family, leading to the identification of a novel role for Rab5a in the endocytosis nectin-2 at adherens junctions of primary human endothelial cells (HUVEC). Confocal microscopy experiments revealed disordered nectin-2 localization at adherens junctions upon Rab5a depletion. In addition, internalized nectin-2 was shown to prominently localize to Rab5a-positive vesicles in both fixed and living cells. As shown previously, nectin-2 stabilization at junctions is achieved via drebrin-dependent coupling to the subcortical actin cytoskeleton. Consistently, depletion of drebrin in this study leads to enhanced internalization of nectin-2 from junctions. Strikingly, simultaneous silencing of Rab5a and drebrin restored the junctional localization of nectin-2, pointing to Rab5a as counteracting the drebrin-dependent stabilization of nectin-2 at adherens junctions. This mechanism could be further validated by transendothelial resistance measurements. Collectively, our results identify Rab5a as a key player in the endocytosis of nectin-2 and thus in the regulation of adherens junction integrity in primary human endothelial cells.Pasquale CerveroKirsten VrenkenMatthias KloseKerstin RehmStefan LinderElsevierarticleAdherens junctionsDrebrinEndocytosisNectinRabGTPasesRab5aCytologyQH573-671ENEuropean Journal of Cell Biology, Vol 100, Iss 7, Pp 151184- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Adherens junctions Drebrin Endocytosis Nectin RabGTPases Rab5a Cytology QH573-671
spellingShingle	Adherens junctions Drebrin Endocytosis Nectin RabGTPases Rab5a Cytology QH573-671 Pasquale Cervero Kirsten Vrenken Matthias Klose Kerstin Rehm Stefan Linder Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis
description	Cell-cell junctions undergo constant remodeling, which is crucial for the control of vascular integrity. Indeed, transport of junctional components such as cadherins is understood in increasing depth. However, little is known about the respective pathways regulating localization of nectin at cell-cell junctions. Here, we performed an siRNA-based screen of vesicle regulators of the RabGTPase family, leading to the identification of a novel role for Rab5a in the endocytosis nectin-2 at adherens junctions of primary human endothelial cells (HUVEC). Confocal microscopy experiments revealed disordered nectin-2 localization at adherens junctions upon Rab5a depletion. In addition, internalized nectin-2 was shown to prominently localize to Rab5a-positive vesicles in both fixed and living cells. As shown previously, nectin-2 stabilization at junctions is achieved via drebrin-dependent coupling to the subcortical actin cytoskeleton. Consistently, depletion of drebrin in this study leads to enhanced internalization of nectin-2 from junctions. Strikingly, simultaneous silencing of Rab5a and drebrin restored the junctional localization of nectin-2, pointing to Rab5a as counteracting the drebrin-dependent stabilization of nectin-2 at adherens junctions. This mechanism could be further validated by transendothelial resistance measurements. Collectively, our results identify Rab5a as a key player in the endocytosis of nectin-2 and thus in the regulation of adherens junction integrity in primary human endothelial cells.
format	article
author	Pasquale Cervero Kirsten Vrenken Matthias Klose Kerstin Rehm Stefan Linder
author_facet	Pasquale Cervero Kirsten Vrenken Matthias Klose Kerstin Rehm Stefan Linder
author_sort	Pasquale Cervero
title	Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis
title_short	Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis
title_full	Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis
title_fullStr	Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis
title_full_unstemmed	Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis
title_sort	nectin stabilization at adherens junctions is counteracted by rab5a-dependent endocytosis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/88195ab62a2d4630bda82262a65d2faa
work_keys_str_mv	AT pasqualecervero nectinstabilizationatadherensjunctionsiscounteractedbyrab5adependentendocytosis AT kirstenvrenken nectinstabilizationatadherensjunctionsiscounteractedbyrab5adependentendocytosis AT matthiasklose nectinstabilizationatadherensjunctionsiscounteractedbyrab5adependentendocytosis AT kerstinrehm nectinstabilizationatadherensjunctionsiscounteractedbyrab5adependentendocytosis AT stefanlinder nectinstabilizationatadherensjunctionsiscounteractedbyrab5adependentendocytosis
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Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis

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