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

Nat. Cell Biol.2015 Mar;17(3):228-240. doi:10.1038/ncb3109. Epub 2015 Feb 16
Quanlong Lu 1 , Christine Insinna 1 , Carolyn Ott 2 , Jimmy Stauffer 1 , Petra A Pintado 3 , Juliati Rahajeng 4 , Ulrich Baxa 5 , Vijay Walia 1 , Adrian Cuenca 1 , Yoo-Seok Hwang 1 , Ira O Daar 1 , Susana Lopes 5 , Jennifer Lippincott-Schwartz 2 , Peter K Jackson 6 , Steve Caplan 4 , Christopher J Westlake 1
Quanlong Lu 1 , Christine Insinna 1 , Carolyn Ott 2 , Jimmy Stauffer 1 , Petra A Pintado 3 , Juliati Rahajeng 4 , Ulrich Baxa 5 , Vijay Walia 1 , Adrian Cuenca 1 , Yoo-Seok Hwang 1 , Ira O Daar 1 , Susana Lopes 5 , Jennifer Lippincott-Schwartz 2 , Peter K Jackson 6 , Steve Caplan 4 , Christopher J Westlake 1
+ et al

[No authors listed]

Author information
  • 1 NCI-Frederick National Laboratory, Laboratory of Cellular and Developmental Signaling, Frederick, MD 21702, USA.
  • 2 Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD.
  • 3 CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
  • 4 Department of Biochemistry and Molecular Biology and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
  • 5 ATRF, NCI-Frederick National Laboratory, Frederick, MD.
  • 6 Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.

摘要

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.

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