溶酶体是细胞降解循环生物大分子物质的重要细胞器。它接收来自包括吞噬等多种囊泡运输途径转运的货物。降解后，氨基酸、糖、核苷酸等生物大分子经由溶酶体膜上转运蛋白运送至胞质中，供细胞再利用。而溶酶体需要经历再形成的过程维持其正常的稳态平衡。
近期，细胞生物学著名期刊The Journal of Cell Biology (JCB) 2019年第8期发表了威尼斯欢乐娱人城AⅤ大中国威尼斯欢乐娱人城AⅤ大中国杨崇林教授实验室的研究论文，题目是The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation。该项研究结果以Article形式在线发表，并被选为封面文章。
JCB封面：吞噬溶酶体再形成的电镜图片
在微分干涉显微镜下，线虫胚胎细胞发生凋亡后呈现出特殊的纽扣状突起形态。杨崇林实验室通过正向遗传学筛选，获得了多个凋亡细胞呈凹坑状的突变体，经克隆发现是由于slc-36.1基因功能缺失突变导致。SLC-36.1蛋白在人类中的同源物是中性氨基酸转运蛋白SLC-36A1。SLC-36.1定位在细胞质膜和溶酶体膜上，而且它的氨基酸转运活性对于其功能是必须的。研究者用绿色荧光蛋白标记溶酶体膜蛋白LAAT-1，用红色荧光蛋白标记溶酶体基质蛋白NUC-1，在荧光显微镜追踪溶酶体在生理条件下的变化过程。在野生型线虫的胚胎中，随着吞噬溶酶体不断伸出丝状结构，并显示有新的溶酶体产生，而吞噬溶酶体的体积不断缩小并最终消失。但是，在slc-36.1突变体的胚胎中，吞噬溶酶体出丝的次数明显减少，并且吞噬溶酶体的体积在很长时间内都保持不变（下图）。因此，SLC-36.1对于溶酶体从吞噬溶酶体上再形成的过程是必需的.
SLC-36.1为溶酶体从吞噬溶酶体上再形成所必需
该研究还发现PPK-3功能缺失同样会阻碍溶酶体从吞噬溶酶体上再形成。PPK-3是磷脂酰肌醇-3-磷酸激酶，能够催化磷脂酰肌醇-3-磷酸继续磷酸化，生成磷脂酰肌醇-3，5-二磷酸，已知磷脂酰肌醇-3，5-二磷酸对于膜分裂起着重要作用。进一步的研究表明，SLC-36.1直接与PPK-3相互作用，形成复合体，协同作用发挥调控作用。研究还发现，在溶酶体从自噬溶酶体上再形成的过程中，SLC-36.1-PPK-3复合物也发挥了调控作用。
SLC-36.1-PPK-3复合物调控溶酶体再形成的模式图
综上所述，本项研究提供的实验证据指明了SLC-36.1-PPK-3复合物在吞噬溶酶体/自噬溶酶体的溶酶体再形成过程中起到了至关重要的调控作用。
据悉，云南生物资源保护与利用国家重点实验室、威尼斯欢乐娱人城AⅤ大中国及威尼斯欢乐娱人城AⅤ大中国为本研究的第一单位。实验室甘启文博士为本文第一作者，国家杰出青年科学基金获得者杨崇林教授为通讯作者。
原文链接：http://jcb.rupress.org/content/early/2019/06/21/jcb.201901074/tab-article-info?versioned=true
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