Nde1 is a Rab9 effector for loading late endosomes to cytoplasmic dynein motor complex.

Yifan Zhang, Ziyue Chen, Fang Wang, Honghua Sun, Xueliang Zhu, Jianping Ding, Tianlong Zhang

Structure (London, England : 1993) 2022 Mar 03

filter terms:

Rab9 is mainly located on late endosomes and required for their intracellular transport to trans-Golgi network (TGN). The cytoplasmic dynein motor, together with its regulatory proteins Nde1/Ndel1 and Lis1, controls intracellular retrograde transport of membranous organelles along the microtubule network. How late endosomes are tethered to the microtubule-based motor dynein for their retrograde transport remains unclear. Here, we demonstrate that the guanosine triphosphate (GTP)-bound Rab9A/B specifically uses Nde1/Ndel1 as an effector to interact with the dynein motor complex. We determined the crystal structure of Rab9A-GTP in complex with the Rab9-binding region of Nde1. The functional roles of key residues involved in the Rab9A-Nde1 interaction are verified using biochemical and cell biology assays. Rab9A mutants unable to bind to Nde1 also failed to associate with dynein, Lis1, and dynactin. Therefore, Nde1 is a Rab9 effector that tethers Rab9-associated late endosomes to the dynein motor for their retrograde transport to the TGN. Copyright © 2021. Published by Elsevier Ltd.

Citation

Yifan Zhang, Ziyue Chen, Fang Wang, Honghua Sun, Xueliang Zhu, Jianping Ding, Tianlong Zhang. Nde1 is a Rab9 effector for loading late endosomes to cytoplasmic dynein motor complex. Structure (London, England : 1993). 2022 Mar 03;30(3):386-395.e5