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SKIP ‐ HOPS recruits TBC 1D15 for a Rab7‐to‐Arl8b identity switch to control late endosome transport
Author(s) -
Jongsma Marlieke LM,
Bakker Jeroen,
Cabukusta Birol,
Liv Nalan,
Elsland Daphne,
Fermie Job,
Akkermans Jimmy LL,
Kuijl Coenraad,
Zanden Sabina Y,
Janssen Lennert,
Hoogzaad Denise,
Kant Rik,
Wijdeven Ruud H,
Klumperman Judith,
Berlin Ilana,
Neefjes Jacques
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019102301
Subject(s) - endosome , biology , microbiology and biotechnology , identity (music) , transport protein , intracellular , physics , acoustics
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 GTP ases 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 , TBC 1D15. Recruitment of TBC 1D15 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.