Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes

Summary: Internalized and ubiquitinated signaling receptors are silenced by their intraluminal budding into multivesicular bodies aided by the endosomal sorting complexes required for transport (ESCRT) machinery. HD-PTP, an ESCRT protein, forms complexes with ESCRT-0, -I and -III proteins, and binds...

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Autores principales:	Jalal M. Kazan, Guillaume Desrochers, Claire E. Martin, Hyeonju Jeong, Dmitri Kharitidi, Pirjo M. Apaja, Ariel Roldan, Nicole St. Denis, Anne-Claude Gingras, Gergely L. Lukacs, Arnim Pause
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Molecular biology Cell biology Science Q
Acceso en línea:	https://doaj.org/article/f8eb2fe20c114718a6151e5c0fe42afc
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spelling	oai:doaj.org-article:f8eb2fe20c114718a6151e5c0fe42afc2021-11-20T05:09:11ZEndofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes2589-004210.1016/j.isci.2021.103274https://doaj.org/article/f8eb2fe20c114718a6151e5c0fe42afc2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012438https://doaj.org/toc/2589-0042Summary: Internalized and ubiquitinated signaling receptors are silenced by their intraluminal budding into multivesicular bodies aided by the endosomal sorting complexes required for transport (ESCRT) machinery. HD-PTP, an ESCRT protein, forms complexes with ESCRT-0, -I and -III proteins, and binds to Endofin, a FYVE-domain protein confined to endosomes with poorly understood roles. Using proximity biotinylation, we showed that Endofin forms a complex with ESCRT constituents and Endofin depletion increased integrin α5-and EGF-receptor plasma membrane density and stability by hampering their lysosomal delivery. This coincided with sustained receptor signaling and increased cell migration. Complementation of Endofin- or HD-PTP-depleted cells with wild-type Endofin or HD-PTP, but not with mutants harboring impaired Endofin/HD-PTP association or cytosolic Endofin, restored EGFR lysosomal delivery. Endofin also promoted Hrs indirect interaction with HD-PTP. Jointly, our results indicate that Endofin is required for HD-PTP and ESCRT-0 interdependent sorting of ubiquitinated transmembrane cargoes to ensure efficient receptor desensitization and lysosomal delivery.Jalal M. KazanGuillaume DesrochersClaire E. MartinHyeonju JeongDmitri KharitidiPirjo M. ApajaAriel RoldanNicole St. DenisAnne-Claude GingrasGergely L. LukacsArnim PauseElsevierarticleBiological sciencesMolecular biologyCell biologyScienceQENiScience, Vol 24, Iss 11, Pp 103274- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Molecular biology Cell biology Science Q
spellingShingle	Biological sciences Molecular biology Cell biology Science Q Jalal M. Kazan Guillaume Desrochers Claire E. Martin Hyeonju Jeong Dmitri Kharitidi Pirjo M. Apaja Ariel Roldan Nicole St. Denis Anne-Claude Gingras Gergely L. Lukacs Arnim Pause Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
description	Summary: Internalized and ubiquitinated signaling receptors are silenced by their intraluminal budding into multivesicular bodies aided by the endosomal sorting complexes required for transport (ESCRT) machinery. HD-PTP, an ESCRT protein, forms complexes with ESCRT-0, -I and -III proteins, and binds to Endofin, a FYVE-domain protein confined to endosomes with poorly understood roles. Using proximity biotinylation, we showed that Endofin forms a complex with ESCRT constituents and Endofin depletion increased integrin α5-and EGF-receptor plasma membrane density and stability by hampering their lysosomal delivery. This coincided with sustained receptor signaling and increased cell migration. Complementation of Endofin- or HD-PTP-depleted cells with wild-type Endofin or HD-PTP, but not with mutants harboring impaired Endofin/HD-PTP association or cytosolic Endofin, restored EGFR lysosomal delivery. Endofin also promoted Hrs indirect interaction with HD-PTP. Jointly, our results indicate that Endofin is required for HD-PTP and ESCRT-0 interdependent sorting of ubiquitinated transmembrane cargoes to ensure efficient receptor desensitization and lysosomal delivery.
format	article
author	Jalal M. Kazan Guillaume Desrochers Claire E. Martin Hyeonju Jeong Dmitri Kharitidi Pirjo M. Apaja Ariel Roldan Nicole St. Denis Anne-Claude Gingras Gergely L. Lukacs Arnim Pause
author_facet	Jalal M. Kazan Guillaume Desrochers Claire E. Martin Hyeonju Jeong Dmitri Kharitidi Pirjo M. Apaja Ariel Roldan Nicole St. Denis Anne-Claude Gingras Gergely L. Lukacs Arnim Pause
author_sort	Jalal M. Kazan
title	Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
title_short	Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
title_full	Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
title_fullStr	Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
title_full_unstemmed	Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
title_sort	endofin is required for hd-ptp and escrt-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/f8eb2fe20c114718a6151e5c0fe42afc
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Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes

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