Investigation of F-BAR domain PACSIN proteins uncovers membrane tubulation function in cilia assembly and transport

• Published in: Nature communications 2019-01, Vol.10 (1), p.428-17, Article 428
• Main Authors: Insinna, Christine, Lu, Quanlong, Teixeira, Isabella, Harned, Adam, Semler, Elizabeth M., Stauffer, Jim, Magidson, Valentin, Tiwari, Ajit, Kenworthy, Anne K., Narayan, Kedar, Westlake, Christopher J.
• Format: Article
• Language: English
• Subjects: 14; 14/19; 14/28; 14/63; 631/80/128/1383; 631/80/313; 64; 64/116; Adaptation; Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Basal Bodies - metabolism; Basal Bodies - ultrastructure; Biodiversity; Biological Transport; Cell Line; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Centrioles - metabolism; Centrioles - ultrastructure; Cilia - metabolism; Cilia - ultrastructure; Climate; Climate change; Embryo, Nonmammalian; Epithelial Cells - metabolism; Epithelial Cells - ultrastructure; Floodplains; Freshwater environments; Gene Expression Regulation; Global warming; Humanities and Social Sciences; Humans; Hydroelectric power; Low flow; Membrane Fusion; Mice; multidisciplinary; NIH 3T3 Cells; Protein Binding; Protein Domains; Rivers; Science; Science (multidisciplinary); Signal Transduction; Snow; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism; Water availability; Zebrafish
• ISSN: 2041-1723; 2041-1723
• 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 tubules from the developing intracellular cilium that attach to the plasma membrane, creating an extracellular membrane channel (EMC) to the outside of the cell. PACSIN proteins are known to mediate membrane tubulation. Here the authors show that PACSIN - positive membranous tubules extend from the ciliary pocket membrane and during ciliogenesis from the ciliary vesicle to the plasma membrane, called extracellular membrane channels (EMCs).