Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
In: iScience, Jg. 24 (2021), Heft 11, S. 103274-
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Zugriff:
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.
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Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
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Autor/in / Beteiligte Person: | Kazan, Jalal M. ; Desrochers, Guillaume ; Martin, Claire E. ; Jeong, Hyeonju ; Kharitidi, Dmitri ; Apaja, Pirjo M. ; Roldan, Ariel ; Nicole St. Denis ; Gingras, Anne-Claude ; Lukacs, Gergely L. ; Pause, Arnim |
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Zeitschrift: | iScience, Jg. 24 (2021), Heft 11, S. 103274- |
Veröffentlichung: | Elsevier, 2021 |
Medientyp: | academicJournal |
ISSN: | 2589-0042 (print) |
DOI: | 10.1016/j.isci.2021.103274 |
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