UVRAG TARGETS THE HOPS COMPLEX

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 自噬和内吞途径是严格调控的膜重排过程，其对于细胞稳态、发育和疾病诱导至关重要。自噬物质通过一个复杂的过程从自噬体传递到溶酶体进行降解，该过程在拓扑学上类似于内体成熟。在这里，我们报告说，Beclin 1结合自噬肿瘤抑制，UVRAG，与HOPS拴系复合物，内体融合机制的关键组成部分相互作用。这种相互作用刺激Rab 7 GT3活性和自噬体与晚期内体和溶酶体融合，从而增强自噬货物递送和降解。此外，UVRAG-HOPS复合物加速细胞内内体-内体融合，导致内吞货物的快速降解。艾滋病相关

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autophagic and endocytic pathways are tightly regulated membrane rearrangement processes that are crucial for cellular homeostasis, development and disease induction. Autophagic cargoes are delivered from autophagosomes to lysosomes for degradation via a complex process that topologically resembles endosomal maturation. Here, we report that a Beclin1-binding autophagic tumour suppressor, UVRAG, interacts with the HOPS tethering complex, a key component of the endosomal fusion machinery. This interaction stimulates Rab7 GTPase activity and autophagosome fusion with late endosomes and lysosomes, thereby enhancing autophagic cargo delivery and degradation. Furthermore, the UVRAG-HOPS complex accelerates intracellular endosome-endosome fusion, resulting in rapid degradation of endocytic cargoes. AIDS related.