SKIP-HOPS recruits TBC1D15 for a Rab7-to-Arl8b identity switch to control late endosome transport

Marlieke L.M. Jongsma, Jeroen Bakker, Birol Cabukusta, Nalan Liv, Daphne van Elsland, Job Fermie, Jimmy L.L. Akkermans, Coenraad Kuijl, Sabina Y. van der Zanden, Lennert Janssen, Denise Hoogzaad, Rik van der Kant, Ruud H. Wijdeven, Judith Klumperman, Ilana Berlin*, Jacques Neefjes

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The endolysosomal system fulfils a myriad of cellular functions predicated on regulated membrane identity progressions, collectively termed maturation. Mature or “late” endosomes are designated by small membrane-bound GTPases Rab7 and Arl8b, which can either operate independently or collaborate to form a joint compartment. Whether, and how, Rab7 and Arl8b resolve this hybrid identity compartment to regain functional autonomy is unknown. Here, we report that Arl8b employs its effector SKIP to instigate inactivation and removal of Rab7 from select membranes. We find that SKIP interacts with Rab7 and functions as its negative effector, delivering the cognate GAP, TBC1D15. Recruitment of TBC1D15 to SKIP occurs via the HOPS complex, whose assembly is facilitated by contacts between Rab7 and the KMI motif of SKIP. Consequently, SKIP mediates reinstatement of single identity Arl8b sub-compartment through an ordered Rab7-to-Arl8b handover, and, together with Rab7's positive effector RILP, enforces spatial, temporal and morphological compartmentalization of endolysosomal organelles.

Original languageEnglish
Article numbere102301
JournalEMBO Journal
Volume39
Issue number6
DOIs
Publication statusPublished - 16 Mar 2020

Cite this

Jongsma, M. L. M., Bakker, J., Cabukusta, B., Liv, N., van Elsland, D., Fermie, J., ... Neefjes, J. (2020). SKIP-HOPS recruits TBC1D15 for a Rab7-to-Arl8b identity switch to control late endosome transport. EMBO Journal, 39(6), [e102301]. https://doi.org/10.15252/embj.2019102301