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bioRxiv · 10.1101/2020.12.22.423978

A WDR35/IFT121-dependent coatomer transports ciliary membrane proteins from the Golgi to the cilia

Quidwai, T.·Hall, E. A.·Keighren, M. A.·Leng, W.·Kiesel, P.·Wells, J. N.·Murphy, L. C.·Marsh, J. A.·Pigino, G.·Mill, P.
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Abstract

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 and across the diffusion barrier 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 IFT-A peripheral components are degraded and core components accumulate at the transition zone. We reveal deep sequence homology and structural similarity of WDR35 and other IFT-As to the coatomer COPI proteins a and {beta}', and demonstrate an accumulation of coat-less vesicles which fail to fuse with Wdr35 mutant cilia. Our data provides the first in situ evidence of a novel coatomer function for WDR35 likely with other IFT-A proteins in delivering ciliary membrane cargo from the Golgi necessary for cilia elongation.

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Quidwai, T., Hall, E. A., Keighren, M. A., Leng, W., Kiesel, P., Wells, J. N., Murphy, L. C., Marsh, J. A., Pigino, G., Mill, P.. 2020-12-23. A WDR35/IFT121-dependent coatomer transports ciliary membrane proteins from the Golgi to the cilia. https://doi.org/10.1101/2020.12.22.423978

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