RabX1 Organizes a Late Endosomal Compartment that Forms Tubular Connections to Lysosomes Consistent with a "Kiss and Run" Mechanism.,Current Biology

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RabX1 Organizes a Late Endosomal Compartment that Forms Tubular Connections to Lysosomes Consistent with a "Kiss and Run" Mechanism.
Current Biology ( IF 8.1 ) Pub Date : 2020-02-05 , DOI: 10.1016/j.cub.2020.01.048
Sara Laiouar ₁ , Nicola Berns ₁ , Andreas Brech ₂ , Veit Riechmann ₁

Affiliation

Degradation of endocytosed proteins involves the formation of transient connections between late endosomes and lysosomes in a process called "kiss and run." Genes and proteins controlling this mechanism are unknown. Here, we identify the small guanosine triphosphatase (GTPase) RabX1 as an organizer of a late endosomal compartment that forms dynamic tubular connections to lysosomes. By analyzing trafficking of the adhesion protein Fasciclin2 in the Drosophila follicular epithelium, we show that a reduction of RabX1 function leads to defects in Fasciclin2 degradation. RabX1 mutants fail to form normal lysosomes and accumulate Fasciclin2 in a swelling late-endosomal compartment. RabX1 protein localizes to late endosomes, where it induces the formation of tubular connections to lysosomes. We propose that these tubules facilitate influx of lysosomal content into late endosomes and that this influx leads to the formation of endolysosomes, in which Fasciclin2 is degraded. We show that the formation of RabX1 tubules is dependent on the V-ATPase proton pump. Moreover, we provide evidence that V-ATPase activity is upregulated during epithelial differentiation. This upregulation intensifies RabX1 tubulation and thereby boosts the capacity of the endolysosomal pathway. Enhanced endolysosomal capacity is required for the removal of Fasciclin2 from the epithelium, which is part of a developmental program promoting epithelial morphogenesis.

中文翻译：

RabX1组织了一个晚期的子宫内膜隔室，该隔室形成了与“亲吻和奔跑”机制一致的溶酶体的管状连接。

内吞蛋白质的降解涉及晚期内体和溶酶体之间的瞬时连接形成，该过程称为“亲吻并运行”。控制这种机制的基因和蛋白质尚不清楚。在这里，我们确定小鸟苷三磷酸酶（GTPase）RabX1是晚期内体室的组织者，后者形成了与溶酶体的动态管状连接。通过分析果蝇卵泡上皮中粘附蛋白Fasciclin2的运输，我们显示RabX1功能的降低导致Fasciclin2降解的缺陷。RabX1突变体无法形成正常的溶酶体，并在肿胀的晚期内膜区室中蓄积Fasciclin2。RabX1蛋白定位于晚期内体，在此处诱导与溶酶体的管状连接的形成。我们建议这些小管促进溶酶体内容物流入晚期内体，并且这种内流导致内胶体的形成，其中Fasciclin2被降解。我们显示，RabX1小管的形成取决于V-ATPase质子泵。此外，我们提供的证据表明上皮细胞分化过程中V-ATPase活性被上调。这种上调增强了RabX1的输卵管，从而增强了溶酶体途径的能力。从上皮中去除Fasciclin2需要增强的溶酶体能力，这是促进上皮形态发生的发展计划的一部分。我们显示，RabX1小管的形成取决于V-ATPase质子泵。此外，我们提供的证据表明上皮细胞分化过程中V-ATPase活性被上调。这种上调增强了RabX1的输卵管，从而增强了溶酶体途径的能力。从上皮中去除Fasciclin2需要增强的溶酶体能力，这是促进上皮形态发生的发展计划的一部分。我们显示，RabX1小管的形成取决于V-ATPase质子泵。此外，我们提供的证据表明上皮细胞分化过程中V-ATPase活性被上调。这种上调增强了RabX1的输卵管，从而增强了溶酶体途径的能力。从上皮中去除Fasciclin2需要增强的溶酶体能力，这是促进上皮形态发生的发展计划的一部分。

更新日期：2020-02-20

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