Biology subjects

Mukhopadhyay, A. G.

Publications and source records attributed to Mukhopadhyay, A. G..

2 recordsLinked to original sources

bioRxiv2023

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

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.

cell biology↗

bioRxiv2022

IFT-A Structure Reveals Carriages for Membrane Protein Transport into Cilia

Intraflagellar transport (IFT) trains are molecular machines that traffic proteins between cilia and the cell body. With a molecular weight over 80 MDa, each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) and motor proteins, posing a formidable challenge to mechanistic understanding. Here, we reconstituted the complete human IFT-A complex and obtained its structure using cryo-EM. Combined with AlphaFold prediction and genome-editing studies, our results illuminate how IFT-A polymerizes; interacts with IFT-B; and uses an array of {beta}-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-A{middle dot}TULP carriages are essential for cilia localization of diverse membrane proteins, as well as ICK - the key kinase regulating IFT train turnaround. These data establish a structural link between IFT-As distinct functions, provide a blueprint for the IFT-A train, and shed light on how IFT evolved from a proto-coatomer ancestor.

cell biology↗