Journal Article

Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation

Hwang, Yoo-Seok, Walia, Vijay, Lopes, Susana, Lu, Quanlong, Ott, Carolyn, Lippincott-Schwartz, Jennifer, Pintado, Petra A., Insinna, Christine, Westlake, Christopher J., Daar, Ira O., Cuenca, Adrian, Caplan, Steve, Baxa, Ulrich, Jackson, Peter K., Stauffer, Jimmy, Rahajeng, Juliati

2015

Overview

Membrane association with mother centriole (M-centriole) distal appendages is critical for ciliogenesis initiation. How the Rab GTPase Rab11–Rab8 cascade functions in early ciliary membrane assembly is unknown. Here, we show that the membrane shaping proteins EHD1 and EHD3, in association with the Rab11–Rab8 cascade, function in early ciliogenesis. EHD1 and EHD3 localize to preciliary membranes and the ciliary pocket. EHD-dependent membrane tubulation is essential for ciliary vesicle formation from smaller distal appendage vesicles (DAVs). Importantly, this step functions in M-centriole to basal body transformation and recruitment of transition zone proteins and IFT20. SNAP29, a SNARE membrane fusion regulator and EHD1-binding protein, is also required for DAV-mediated ciliary vesicle assembly. Interestingly, only after ciliary vesicle assembly is Rab8 activated for ciliary growth. Our studies uncover molecular mechanisms informing a previously uncharacterized ciliogenesis step, whereby EHD1 and EHD3 reorganize the M-centriole and associated DAVs before coordinated ciliary membrane and axoneme growth. Westlake and colleagues discover that membrane shaping EHD proteins participate in ciliogenesis by taking part in ciliary vesicle formation and transition zone protein recruitment.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/109 / 13/89 / 14 / 14/19 / 14/28 / 14/35 / 38/1 / 631/136/2432 / 631/80/128/1383 / 631/80/313 / 64/116 / 82/80 / Animals / Axoneme - metabolism / Axoneme - ultrastructure / Cancer Research / Carrier Proteins - antagonists & inhibitors / Carrier Proteins - genetics / Carrier Proteins - metabolism / Cell Biology / Cell Line / Cell organelles / Cell research / Centrioles - metabolism / Centrioles - ultrastructure / Cilia - metabolism / Cilia - ultrastructure / Cilia and ciliary motion / Developmental Biology / Embryo, Nonmammalian / Epithelial Cells - metabolism / Epithelial Cells - ultrastructure / Formation / Gene Expression Regulation, Developmental / Humans / Kidney Tubules, Collecting - metabolism / Kidney Tubules, Collecting - ultrastructure / Life Sciences / Membrane proteins / Membranes / Mice / Morphogenesis - genetics / Physiological aspects / Properties / Qb-SNARE Proteins - genetics / Qb-SNARE Proteins - metabolism / Qc-SNARE Proteins - genetics / Qc-SNARE Proteins - metabolism / rab GTP-Binding Proteins - genetics / rab GTP-Binding Proteins - metabolism / Retinal Pigment Epithelium - metabolism / Retinal Pigment Epithelium - ultrastructure / RNA, Small Interfering - genetics / RNA, Small Interfering - metabolism / Signal Transduction / Stem Cells / Transport Vesicles - metabolism / Transport Vesicles - ultrastructure / Vesicular Transport Proteins - antagonists & inhibitors / Vesicular Transport Proteins - genetics / Vesicular Transport Proteins - metabolism / Zebrafish