PIKfyve activity regulates reformation of terminal storage lysosomes from endolysosomes
PIKfyve activity regulates reformation of terminal storage lysosomes from endolysosomes
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DOI：
10.1111/tra.12525
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发表时间：
2017-11-01
期刊：
影响因子：
4.5
通讯作者：
van Niel, Guillaume
中科院分区：
文献类型：
--
作者：
Bissig, Christin;Hurbain, Ilse;van Niel, Guillaume
由激酶PIKfyve、磷酸酶FIG 4和支架蛋白VAC 14组成的蛋白质复合物调节磷脂酰肌醇3，5-二磷酸的代谢，磷脂酰肌醇3，5-二磷酸充当信号脂质和磷脂酰肌醇5-磷酸的主要前体。该复合物参与晚期内吞隔室的稳态，但其在维持晚期内体、内溶酶体和溶酶体的动态平衡中的确切作用仍有待确定。在这里，我们报告了PIKfyve活性的抑制损害了末端溶酶体从酸性和水解酶活性的再形成，但扩大了内溶酶体。我们的活细胞成像和电子断层扫描数据显示，PIKfyve活性调节广泛的膜重塑，启动溶酶体从内溶酶体的重组。总之，我们的研究结果表明，PIKfyve活性需要通过调节终末储存溶酶体的重组来维持晚期内吞隔室的动态平衡。
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.