Inhibition of endolysosome fusion increases exosome secretion.
Inhibition of endolysosome fusion increases exosome secretion.
复制标题
内溶酶体融合的抑制增加外泌体分泌。
DOI：
10.1083/jcb.202209084
复制
发表时间：
2023-06-05
影响因子：
7.8
通讯作者：
Bonifacino, Juan S.
中科院分区：
文献类型：
--
作者：
Shelke, Ganesh Vilas;Williamson, Chad D.;Jarnik, Michal;Bonifacino, Juan S.
Shelke等人表明，BORC-ARL 8-HOPS途径的破坏通过损害多泡内体与溶酶体的融合来增加外泌体分泌，从而增加管腔内囊泡释放到细胞外空间的可用性。外泌体是细胞分泌的小囊泡，用于处理未降解物质并介导细胞间通讯。外泌体的主要来源是多泡内体内的腔内囊泡，其经历与质膜的外泌融合。多囊内体的另一种命运是与溶酶体融合，导致腔内囊泡降解。决定多泡内体是与质膜融合还是与溶酶体融合的因素尚不清楚。在这项研究中，我们表明，通过破坏涉及BLOC-1-相关复合物（BORC），小GTTARL 8和拴系因子HOPS的途径，通过阻止向溶酶体递送腔内囊泡来增加外泌体分泌，从而损害内溶酶体融合。这些发现表明，内溶酶体融合是外泌体分泌量的关键决定因素，并表明BORC-ARL 8-HOPS途径的抑制可用于提高生物技术应用中的外泌体产量。
Shelke et al. show that disruption of the BORC–ARL8–HOPS pathway increases exosome secretion by impairing fusion of multivesicular endosomes with lysosomes, and thus increasing the availability of intraluminal vesicles for release into the extracellular space. Exosomes are small vesicles that are secreted from cells to dispose of undegraded materials and mediate intercellular communication. A major source of exosomes is intraluminal vesicles within multivesicular endosomes that undergo exocytic fusion with the plasma membrane. An alternative fate of multivesicular endosomes is fusion with lysosomes, resulting in degradation of the intraluminal vesicles. The factors that determine whether multivesicular endosomes fuse with the plasma membrane or with lysosomes are unknown. In this study, we show that impairment of endolysosomal fusion by disruption of a pathway involving the BLOC-one-related complex (BORC), the small GTPase ARL8, and the tethering factor HOPS increases exosome secretion by preventing the delivery of intraluminal vesicles to lysosomes. These findings demonstrate that endolysosomal fusion is a critical determinant of the amount of exosome secretion and suggest that suppression of the BORC–ARL8–HOPS pathway could be used to boost exosome yields in biotechnology applications.
登录
查看更多内容
影响因子：
9.2
作者：
Bright, Nicholas A.;Davis, Luther J.;Luzio, J. Paul
通讯作者：
Luzio, J. Paul
溶酶体胆固醇通过 NPC2 排出需要 BORC-ARL8-HOPS 组合。
影响因子：
3.3
作者：
Anderson, Jacob;Walker, Gerard;Pu, Jing
通讯作者：
Pu, Jing
影响因子：
3.3
作者：
Nakae I;Fujino T;Kobayashi T;Sasaki A;Kikko Y;Fukuyama M;Gengyo-Ando K;Mitani S;Kontani K;Katada T
通讯作者：
Katada T
影响因子：
32.4
作者：
Garg S;Sharma M;Ung C;Tuli A;Barral DC;Hava DL;Veerapen N;Besra GS;Hacohen N;Brenner MB
通讯作者：
Brenner MB
影响因子：
6.7
作者：
Aharon, Anat;Tamari, Tal;Brenner, Benjamin
通讯作者：
Brenner, Benjamin