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

• Published in: eLife Vol. 10
• Main Authors: Quidwai, Tooba, Wang, Jiaolong, Hall, Emma A, Petriman, Narcis A, Leng, Weihua, Kiesel, Petra, Wells, Jonathan N, Murphy, Laura C, Keighren, Margaret A, Marsh, Joseph A, Lorentzen, Esben, Pigino, Gaia, Mill, Pleasantine
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 04.11.2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Cell Biology; Cells; Chlamydomonas reinhardtii - metabolism; Cilia; Cilia - metabolism; ciliary pocket; Coat protein; coatomer; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Fibroblasts; Gene mutations; Homology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; intraflagellar transport; Lipids; Localization; membrane cargos; Membrane lipids; Membrane proteins; Membrane vesicles; Membranes; Mice; Microscopy; Mutants; Mutation; Protein Binding; Protein Transport; Proteins; Retrograde transport; Satellites; vesicular traffic; membrane cargos; chlamydomonas reinhardtii; intraflagellar transport; CLEM; coatomer; vesicular traffic; mouse; cell biology; correlative light and electron microscopy; IFT; COPI; cilia; transmission electron microscopy; TEM; ciliary pocket
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.69786

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 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 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.