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

• Marlieke LM Jongsma ^[1] ; Jeroen Bakker ^[1] ; Birol Cabukusta ^[1] ; Nalan Liv ^[3] ; Daphne van Elsland ^[1] ; Job Fermie ^[3] ; Jimmy LL Akkermans ^[1] ; Coenraad Kuijl ^[2] ; Sabina Y van der Zanden ^[1] ; Lennert Janssen ^[1] ; Denise Hoogzaad ^[1] ; Rik van der Kant ^[4] ; Ruud H Wijdeven ^[1] ; Judith Klumperman ^[3] ; Ilana Berlin ^[1] ; Jacques Neefjes ^[1]
  1. [1] Leiden University Medical Center

     Leiden University Medical Center

     Países Bajos

     
  2. [2] VU University Medical Center

     VU University Medical Center

     Países Bajos

     
  3. [3] 3 Section Cell Biology Center for Molecular Medicine University Medical Center Utrecht Utrecht The Netherlands
  4. [4] 5 Center for Neurogenomics and Cognitive Research Faculty of Sciences VU Amsterdam Amsterdam The Netherlands

  Mostrar afiliaciones +
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 39, Nº. 6, 2020
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • 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.