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DYNLRB1 is essential for dynein mediated transport and neuronal survival.

Authors
  • Terenzio, Marco1
  • Di Pizio, Agostina2
  • Rishal, Ida2
  • Marvaldi, Letizia2
  • Di Matteo, Pierluigi2
  • Kawaguchi, Riki3
  • Coppola, Giovanni3
  • Schiavo, Giampietro4
  • Fisher, Elizabeth M C5
  • Fainzilber, Mike2
  • 1 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel; Molecular Neuroscience Unit, Okinawa Institute of Science and Technology Graduate University, Kunigami-gun, Okinawa 904-0412, Japan. Electronic address: [email protected] , (Israel)
  • 2 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. , (Israel)
  • 3 Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • 4 Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1E 6BT, UK; Discoveries Centre for Regenerative and Precision Medicine, University College London Campus, London WC1N 3BG, UK.
  • 5 Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Type
Published Article
Journal
Neurobiology of Disease
Publisher
Elsevier
Publication Date
Jul 01, 2020
Volume
140
Pages
104816–104816
Identifiers
DOI: 10.1016/j.nbd.2020.104816
PMID: 32088381
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The cytoplasmic dynein motor complex transports essential signals and organelles from the cell periphery to the perinuclear region, hence is critical for the survival and function of highly polarized cells such as neurons. Dynein Light Chain Roadblock-Type 1 (DYNLRB1) is thought to be an accessory subunit required for specific cargos, but here we show that it is essential for general dynein-mediated transport and sensory neuron survival. Homozygous Dynlrb1 null mice are not viable and die during early embryonic development. Furthermore, heterozygous or adult knockdown animals display reduced neuronal growth, and selective depletion of Dynlrb1 in proprioceptive neurons compromises their survival. Conditional depletion of Dynlrb1 in sensory neurons causes deficits in several signaling pathways, including β-catenin subcellular localization, and a severe impairment in the axonal transport of both lysosomes and retrograde signaling endosomes. Hence, DYNLRB1 is an essential component of the dynein complex, and given dynein's critical functions in neuronal physiology, DYNLRB1 could have a prominent role in the etiology of human neurodegenerative diseases. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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