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.

中文翻译：

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SKIP-HOPS招募TBC1D15用于Rab7-to-Arl8b身份转换，以控制晚期内体运输。

溶酶体系统可完成多种细胞功能，这些功能取决于调节的膜特性进程，统称为成熟。成熟的或“晚期”的内体由膜结合的小GTPases Rab7和Arl8b表示，它们既可以独立运行，也可以共同形成关节腔。Rab7和Arl8b是否以及如何解析此混合身份隔离区以重新获得功能自主权，尚不得而知。在这里，我们报告说，Arl8b利用其效应器SKIP促使Rab7从选定的膜中失活和去除。我们发现SKIP与Rab7相互作用并充当其负效应子，提供相关的GAP TBC1D15。通过HOPS复合体将TBC1D15招募到SKIP，Rab7与SKIP的KMI主题之间的接触促进了其组装。所以，