School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
Nat Commun. 2019 Jul 19;10(1):3218. doi: 10.1038/s41467-019-11056-5.
Proteins are transported among eukaryotic organelles along the cytoskeleton in membrane carriers. The mechanism regarding the motility of carriers and the positioning of organelles is a fundamental question in cell biology that remains incompletely understood. Here, we find that Dopey1 and Mon2 assemble into a complex and localize to the Golgi, endolysosome and endoplasmic reticulum exit site. The Golgi localization of Dopey1 and Mon2 requires their binding to phosphatidylinositol-4-phosphate and phosphatidic acid, respectively, two lipids known for the biogenesis of membrane carriers and the specification of organelle identities. The N-terminus of Dopey1 further interacts with kinesin-1, a plus-end or centrifugal-direction microtubule motor. Dopey1-Mon2 complex functions as a dual-lipid-regulated cargo-adaptor to recruit kinesin-1 to secretory and endocytic organelles or membrane carriers for centrifugally biased bidirectional transport. Dopey1-Mon2 complex therefore provides an important missing link to coordinate the budding of a membrane carrier and subsequent bidirectional transport along the microtubule.
蛋白质沿着细胞骨架在膜载体中在真核细胞器之间运输。载体的运动和细胞器的定位的机制是细胞生物学中的一个基本问题，目前仍不完全了解。在这里，我们发现 Dopey1 和 Mon2 组装成一个复合物，并定位于高尔基体、内溶酶体和内质网出口部位。Dopey1 和 Mon2 的高尔基体定位分别需要它们与磷酸肌醇-4-磷酸和磷脂酸结合，这两种脂质分别参与膜载体的生物发生和细胞器身份的指定。Dopey1 的 N 端进一步与驱动蛋白-1 相互作用，驱动蛋白-1 是一种正极或离心方向的微管马达。Dopey1-Mon2 复合物作为一种双脂质调节的货物衔接物，将驱动蛋白-1募集到分泌和内吞细胞器或膜载体，以进行离心偏向的双向运输。因此，Dopey1-Mon2 复合物提供了一个重要的缺失环节，以协调膜载体的出芽和随后沿着微管的双向运输。
