A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion.
A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion.
复制标题
磷酸肌醇开关介导外囊肿募集到多囊内体进行外泌体分泌。
DOI：
10.1038/s41467-023-42661-0
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发表时间：
2023-10-28
影响因子：
16.6
通讯作者：
Guo, Wei
中科院分区：
文献类型：
--
作者：
Liu, Di-Ao;Tao, Kai;Wu, Bin;Yu, Ziyan;Szczepaniak, Malwina;Rames, Matthew;Yang, Changsong;Svitkina, Tatyana;Zhu, Yueyao;Xu, Fengyuan;Nan, Xiaolin;Guo, Wei
当多囊泡内小体(MVEs)与质膜对接和融合时，外小体被分泌到细胞外环境。然而，已知的是，血管内皮也可以与溶酶体融合以进行降解。目前尚不清楚血管内皮细胞如何被导向质膜以分泌外切体，而不是被导向溶酶体。在此，我们报道了肌管蛋白1(MTM1)和磷脂酰肌醇4-激酶IIα(PI4KIIα)依次催化磷脂酰肌醇-3-磷酸(PI(3)P)转化为磷脂酰肌醇-4-磷酸(PI(4)P)，介导了外囊复合体的募集。然后，外囊将血管内皮细胞定位到质膜上，进行外体分泌。我们进一步证明，破坏PI(4)P的产生或胞外功能阻止了肿瘤细胞中关键的免疫检查点蛋白PD-L1的胞外分泌，并导致其在溶酶体中积累。综上所述，我们的研究表明，血管上的PI(3)P向PI(4)P的转化和胞外囊泡的募集指导了血管内皮细胞的胞外转运以获得胞外体的分泌。外切体从细胞中释放的分子机制尚不清楚。在这里，作者报道了磷脂酰肌醇的转化将八聚体外囊复合体招募到多囊内体以进行外体分泌。
Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion. The molecular mechanism by which exosomes are released from cells is unclear. Here the authors report that a phosphatidylinositide conversion couples the recruitment of the octameric exocyst complex to multivesicular endosomes for exosome secretion.
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影响因子：
11.8
作者：
Barman, Bahnisikha;Sung, Bong Hwan;Krystofiak, Evan;Ping, Jie;Ramirez, Marisol;Millis, Bryan;Allen, Ryan;Prasad, Nripesh;Chetyrkin, Sergei;Calcutt, M. Wade;Vickers, Kasey;Patton, James G.;Liu, Qi;Weaver, Alissa M.
通讯作者：
Weaver, Alissa M.
影响因子：
4.6
作者：
Creech, Matthew K.;Wang, Jing;Gibbs, Summer L.
通讯作者：
Gibbs, Summer L.
影响因子：
16.6
作者：
Civitci, Fehmi;Shangguan, Julia;Nan, Xiaolin
通讯作者：
Nan, Xiaolin
影响因子：
16.8
作者：
Heider MR;Gu M;Duffy CM;Mirza AM;Marcotte LL;Walls AC;Farrall N;Hakhverdyan Z;Field MC;Rout MP;Frost A;Munson M
通讯作者：
Munson M
DOI：
10.1111/j.1600-0854.2012.01353.x
发表时间：
2012-07
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Heider MR;Munson M
通讯作者：
Munson M