A WDR35-dependent coat protein complex transports ciliary membrane cargo vesicles to cilia

eLife

Narcis A Petriman¹  Jiaolong Wang¹  Esben Lorentzen¹  Tooba Quidwai²  Laura C Murphy²  Margaret A Keighren²  Emma A Hall²  Pleasantine Mill²  Joseph A Marsh²  Jonathan N Wells²  Petra Kiesel³  Weihua Leng³  Gaia Pigino⁴ 

[1] Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark;MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom;Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany;Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany;Human Technopole, Milan, Italy;

关键词: cilia;    intraflagellar transport;    ciliary pocket;    membrane cargos;    vesicular traffic;    coatomer;    COPI;    transmission electron microscopy;    correlative light and electron microscopy;    IFT;    TEM;    CLEM;    Chlamydomonas reinhardtii;    Mouse;   

DOI  :  10.7554/eLife.69786

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Intraflagellar transport (IFT) is a highly conserved mechanism for motor-driven transport of cargo within cilia, but how this cargo is selectively transported to cilia is unclear. WDR35/IFT121 is a component of the IFT-A complex best known for its role in ciliary retrograde transport. In the absence of WDR35, small mutant cilia form but fail to enrich in diverse classes of ciliary membrane proteins. In Wdr35 mouse mutants, the non-core IFT-A components are degraded and core components accumulate at the ciliary base. We reveal deep sequence homology of WDR35 and other IFT-A subunits to α and ß′ COPI coatomer subunits and demonstrate an accumulation of ‘coat-less’ vesicles that fail to fuse with Wdr35 mutant cilia. We determine that recombinant non-core IFT-As can bind directly to lipids and provide the first in situ evidence of a novel coat function for WDR35, likely with other IFT-A proteins, in delivering ciliary membrane cargo necessary for cilia elongation.

【 授权许可】

CC BY