Law Fiona, Rocheleau Christian E
Division of Endocrinology and Metabolism, Department of Medicine and the Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Program in Metabolic Disorders and Complications, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Cell Logist. 2017 Dec 19;7(4):e1403530. doi: 10.1080/21592799.2017.1403530. eCollection 2017.
Rab5 and Rab7 GTPases are key regulators of endosome maturation and lysosome fusion. They activate the class III phosphoinositide 3-kinase (PI3K) Vps34 to generate pools of phosphatidylinositol-3 phosphate [PI(3)P] on endosomes. Together PI(3)P and the GTP-bound Rabs coordinate the recruitment of endosomal regulators to drive early to late endosome maturation and ultimately lysosome fusion. Counterintuitively, loss of Vps34 results in enlarged endosomes, like those seen from expressing activated Rab GTPases. Two recent papers in the , Jaber , 2016 and Law, Seo ., 2017, demonstrate that a function of Vps34 is to inactive the Rab5 and Rab7 GTPases via recruitment of the TBC1D2 family of Rab GTPase Activating Proteins (GAPs).
Rab5和Rab7 GTP酶是内体成熟和溶酶体融合的关键调节因子。它们激活III类磷酸肌醇3激酶（PI3K）Vps34，在内体上生成磷脂酰肌醇-3-磷酸[PI(3)P]池。PI(3)P和结合GTP的Rabs共同协调内体调节因子的募集，以驱动早期到晚期内体成熟并最终实现溶酶体融合。与直觉相反，Vps34的缺失会导致内体增大，就像表达活化的Rab GTP酶时看到的那样。《自然》杂志2016年发表的Jaber等人以及2017年发表的Law、Seo等人的两篇近期论文表明，Vps34的一个功能是通过募集Rab GTP酶激活蛋白（GAP）的TBC1D2家族来使Rab5和Rab7 GTP酶失活。
