BORC, a multisubunit complex that regulates lysosome positioning.
BORC, a multisubunit complex that regulates lysosome positioning.
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DOI：
10.1016/j.devcel.2015.02.011
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发表时间：
2015-04-20
影响因子：
11.8
通讯作者：
Bonifacino JS
中科院分区：
文献类型：
--
作者：
Pu J;Schindler C;Jia R;Jarnik M;Backlund P;Bonifacino JS
溶酶体在细胞质内的定位是许多溶酶体功能的关键决定因素。在这里，我们报告了一个多亚基复合物BORC，调节溶酶体定位的鉴定。BORC包含八个亚基，其中一些与参与溶酶体相关细胞器的生物发生的BLOC-1复合物共享，而其他亚基是先前未表征的开放阅读框架的产物。BORC在外周与溶酶体膜结合，在溶酶体膜处其功能是募集小的GTdR Arl 8。这启动了一系列相互作用，促进溶酶体向外周细胞质中微管的正端运动的驱动蛋白-1依赖性运动。干扰BORC或该途径的其他组分会导致溶酶体群塌陷到中心粒周围区域。反过来，这导致细胞扩散和迁移减少，突出了BORC依赖性离心转运对溶酶体非降解功能的重要性。
The positioning of lysosomes within the cytoplasm is emerging as a critical determinant of many lysosomal functions. Here we report the identification of a multi-subunit complex named BORC that regulates lysosome positioning. BORC comprises eight subunits, some of which are shared with the BLOC-1 complex involved in the biogenesis of lysosome-related organelles, and the others of which are products of previously uncharacterized open reading frames. BORC associates peripherally with the lysosomal membrane, where it functions to recruit the small GTPase Arl8. This initiates a chain of interactions that promotes the Kinesin-1-dependent movement of lysosomes toward the plus ends of microtubules in the peripheral cytoplasm. Interference with BORC or other components of this pathway results in collapse of the lysosomal population into the pericentriolar region. In turn, this causes reduced cell spreading and migration, highlighting the importance of BORC-dependent centrifugal transport for non-degradative functions of lysosomes.