The eukaryotic endomembrane system consists of multiple interconnected organelles. Rab GTPases are organelle-specific markers that give identity to these membranes by recruiting transport and trafficking proteins. During transport processes or along organelle maturation, one Rab is replaced by another, a process termed Rab cascade, which requires at its center a Rab-specific guanine nucleotide exchange factor (GEF). The endolysosomal system serves here as a prime example for a Rab cascade. Along with endosomal maturation, the endosomal Rab5 recruits and activates the Rab7-specific GEF Mon1-Ccz1, resulting in Rab7 activation on endosomes and subsequent fusion of endosomes with lysosomes. In this review, we focus on the current idea of Mon1-Ccz1 recruitment and activation in the endolysosomal and autophagic pathway. We compare identified principles to other GTPase cascades on endomembranes, highlight the importance of regulation, and evaluate in this context the strength and relevance of recent developments in in vitro analyses to understand the underlying foundation of organelle biogenesis and maturation.

中文翻译：

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谁在掌控？Rab GTPase 在内溶酶体膜运输及其他方面激活的原理

真核内膜系统由多个相互连接的细胞器组成。Rab GTP 酶是细胞器特异性标记，通过招募转运和运输蛋白来识别这些膜。在运输过程中或细胞器成熟过程中，一种 Rab 被另一种取代，这一过程称为 Rab 级联，其中心需要 Rab 特异性鸟嘌呤核苷酸交换因子 (GEF)。内溶酶体系统在这里作为 Rab 级联的一个主要例子。随着内体成熟，内体 Rab5 招募并激活 Rab7 特异性 GEF Mon1-Ccz1，导致内体上的 Rab7 激活以及随后内体与溶酶体的融合。在这篇综述中，我们重点关注目前关于 Mon1-Ccz1 在内溶酶体和自噬途径中招募和激活的观点。我们将已确定的原理与内膜上的其他 GTP 酶级联进行比较，强调调节的重要性，并在此背景下评估体外分析最新进展的强度和相关性，以了解细胞器生物发生和成熟的根本基础。