Laboratory of Cellular and Developmental Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21701, USA.
Nat Commun. 2019 Jan 25;10(1):428. doi: 10.1038/s41467-018-08192-9.
The intracellular ciliogenesis pathway requires membrane trafficking, fusion, and reorganization. Here, we demonstrate in human cells and zebrafish that the F-BAR domain containing proteins PACSIN1 and -2 play an essential role in ciliogenesis, similar to their binding partner and membrane reorganizer EHD1. In mature cilia, PACSINs and EHDs are dynamically localized to the ciliary pocket membrane (CPM) and transported away from this structure on membrane tubules along with proteins that exit the cilium. PACSINs function early in ciliogenesis at the ciliary vesicle (CV) stage to promote mother centriole to basal body transition. Remarkably, we show that PACSIN1 and EHD1 assemble membrane t7ubules from the developing intracellular cilium that attach to the plasma membrane, creating an extracellular membrane channel (EMC) to the outside of the cell. Together, our work uncovers a function for F-BAR proteins and membrane tubulation in ciliogenesis and explains how the intracellular cilium emerges from the cell.
细胞内纤毛发生途径需要膜运输、融合和重排。在这里,我们在人类细胞和斑马鱼中证明,含有 F-BAR 结构域的蛋白 PACSIN1 和 -2 在纤毛发生中发挥着重要作用,这与它们的结合伙伴和膜重排蛋白 EHD1 相似。在成熟的纤毛中,PACSINs 和 EHDs 动态定位于纤毛口袋膜(CPM),并沿着膜小管从该结构运输到离开纤毛的蛋白质。PACSINs 在纤毛泡(CV)阶段的早期纤毛发生中起作用,以促进母中心粒向基体的转变。值得注意的是,我们表明 PACSIN1 和 EHD1 从发育中的细胞内纤毛组装膜小管,附着在质膜上,在细胞外部形成一个细胞外膜通道(EMC)。总之,我们的工作揭示了 F-BAR 蛋白和膜小管在纤毛发生中的作用,并解释了细胞内纤毛是如何从细胞中出现的。