Institut Curie, PSL Research University, CNRS, UMR144, Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 144, Paris, France.
Traffic. 2017 Nov;18(11):747-757. doi: 10.1111/tra.12525.
The protein complex composed of the kinase PIKfyve, the phosphatase FIG4 and the scaffolding protein VAC14 regulates the metabolism of phosphatidylinositol 3,5-bisphosphate, which serves as both a signaling lipid and the major precursor for phosphatidylinositol 5-phosphate. This complex is involved in the homeostasis of late endocytic compartments, but its precise role in maintaining the dynamic equilibrium of late endosomes, endolysosomes and lysosomes remains to be determined. Here, we report that inhibition of PIKfyve activity impairs terminal lysosome reformation from acidic and hydrolase-active, but enlarged endolysosomes. Our live-cell imaging and electron tomography data show that PIKfyve activity regulates extensive membrane remodeling that initiates reformation of lysosomes from endolysosomes. Altogether, our findings show that PIKfyve activity is required to maintain the dynamic equilibrium of late endocytic compartments by regulating the reformation of terminal storage lysosomes.
由激酶 PIKfyve、磷酸酶 FIG4 和支架蛋白 VAC14 组成的蛋白质复合物调节了磷脂酰肌醇 3,5-二磷酸的代谢，该物质既是信号脂质，也是磷脂酰肌醇 5-磷酸的主要前体。该复合物参与了晚期内体区室的动态平衡，但它在维持晚期内体、溶酶体和溶酶体之间的动态平衡中的精确作用仍有待确定。在这里，我们报告说，抑制 PIKfyve 的活性会损害从酸性和水解酶活性但体积增大的溶酶体中重新形成终末溶酶体。我们的活细胞成像和电子断层扫描数据表明，PIKfyve 的活性调节广泛的膜重塑，从而启动从溶酶体中重新形成溶酶体。总之，我们的研究结果表明，PIKfyve 的活性通过调节终末储存溶酶体的形成来维持晚期内体区室的动态平衡。
