Endofin is Required for HD-PTP and ESCRT-0 Interdependent Endosomal Sorting of Ubiquitinated Transmembrane Cargoes.

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dc.contributor.authorKazan, J.M.
dc.contributor.authorDesrochers, G.
dc.contributor.authorMartin, C.E.
dc.contributor.authorJeong, H.
dc.contributor.authorKharitidi, D.
dc.contributor.authorApaja, P.M.
dc.contributor.authorRoldan, A.
dc.contributor.authorSt. Denis, N.
dc.contributor.authorGingras, A.-C.
dc.contributor.authorLukacs, G.L.
dc.contributor.authorPause, A.
dc.date.issued2021
dc.description.abstractInternalized 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 a5-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.
dc.description.statementofresponsibilityJalal 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, and Arnim Pause
dc.identifier.citationiScience, 2021; 24(11):103274-1-103274-27
dc.identifier.doi10.1016/j.isci.2021.103274
dc.identifier.issn2589-0042
dc.identifier.issn2589-0042
dc.identifier.orcidApaja, P.M. [0000-0002-1622-2332]
dc.identifier.urihttps://hdl.handle.net/2440/146201
dc.language.isoen
dc.publisherElsevier BV
dc.rights© 2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.source.urihttps://doi.org/10.1016/j.isci.2021.103274
dc.subjectsignaling receptors; endosomal sorting complexes required for transport (ESCRT) machinery; HD-PTP; ESCRT-0, -I, -III proteins; Endofin; endosomes; cell migration; cells
dc.titleEndofin is Required for HD-PTP and ESCRT-0 Interdependent Endosomal Sorting of Ubiquitinated Transmembrane Cargoes.
dc.typeJournal article
pubs.publication-statusPublished

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