Roles for CEP170 in cilia function and dynein-2 assembly.

Weijman, J. F.; Vuolo, L.; Shak, C.; Pugnetti, A.; Mukhopadhyay, A. G.; Hodgson, L. R.; Heesom, K. J.; Roberts, A. J.; Stephens, D. J.

doi:10.1101/2023.11.20.567836

bioRxiv · 10.1101/2023.11.20.567836

Roles for CEP170 in cilia function and dynein-2 assembly.

Weijman, J. F.·Vuolo, L.·Shak, C.·Pugnetti, A.·Mukhopadhyay, A. G.·Hodgson, L. R.·Heesom, K. J.·Roberts, A. J.·Stephens, D. J.

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Abstract

Primary cilia are essential eukaryotic organelles required for signalling and secretion. Dynein-2 is a microtubule-motor protein complex and is required for ciliogenesis via its role in facilitating retrograde intraflagellar transport from the cilia tip to the cell body. Dynein-2 must be assembled and loaded onto IFT-trains for entry into cilia for this process to occur but how dynein-2 is assembled at the base and how it is recycled back into a cilium remain poorly understood. Here, we identify Centrosomal Protein of 170 kDa (CEP170) as a dynein-2 interacting protein. We show that loss of CEP170 perturbs intraflagellar transport, Hedgehog signalling, and alters the stability of dynein-2 holoenzyme complex. Together, our data indicate a role for CEP170 in supporting cilia function and dynein-2 assembly. SummaryIntraflagellar transport is required for the function of primary cilia. In this work, we show that Centrosomal Protein 170 (CEP170) interacts with the IFT motor dynein-2 and loss of CEP170 causes defects in dynein-2 assembly and cilia function.

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Weijman, J. F., Vuolo, L., Shak, C., Pugnetti, A., Mukhopadhyay, A. G., Hodgson, L. R., Heesom, K. J., Roberts, A. J., Stephens, D. J.. 2023-11-21. Roles for CEP170 in cilia function and dynein-2 assembly.. https://doi.org/10.1101/2023.11.20.567836

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