Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
J Cell Biol. 2024 Dec 2;223(12). doi: 10.1083/jcb.202311189. Epub 2024 Sep 27.
Mutations in VPS13B, a member of a protein family implicated in bulk lipid transport between adjacent membranes, cause Cohen syndrome. VPS13B is known to be concentrated in the Golgi complex, but its precise location within this organelle and thus the site(s) where it achieves lipid transport remains unclear. Here, we show that VPS13B is localized at the interface between proximal and distal Golgi subcompartments and that Golgi complex reformation after Brefeldin A (BFA)-induced disruption is delayed in VPS13B KO cells. This delay is phenocopied by the loss of FAM177A1, a Golgi complex protein of unknown function reported to be a VPS13B interactor and whose mutations also result in a developmental disorder. In zebrafish, the vps13b ortholog, not previously annotated in this organism, genetically interacts with fam177a1. Collectively, these findings raise the possibility that bulk lipid transport by VPS13B may play a role in the dynamics of Golgi membranes and that VPS13B may be assisted in this function by FAM177A1.
VPS13B 基因突变会导致 Cohen 综合征，该基因是一个参与相邻膜之间大量脂质运输的蛋白家族的成员。已知 VPS13B 集中在高尔基体复合物中，但它在这个细胞器中的精确位置，以及它实现脂质运输的位置尚不清楚。在这里，我们表明 VPS13B 定位于近端和远端高尔基体亚区之间的界面，并且在 Brefeldin A（BFA）诱导的破坏后，VPS13B KO 细胞中的高尔基体复合物重构被延迟。这种延迟与 FAM177A1 的缺失相类似，FAM177A1 是一种功能未知的高尔基体复合物蛋白，据报道是 VPS13B 的相互作用蛋白，其突变也导致发育障碍。在斑马鱼中，vps13b 同源物，在这个生物体中以前没有注释，与 fam177a1 在遗传上相互作用。总的来说，这些发现提出了这样一种可能性，即 VPS13B 的大量脂质运输可能在高尔基体膜的动力学中发挥作用，并且 FAM177A1 可能协助 VPS13B 发挥此功能。
