DYNLRB1 is essential for dynein mediated transport and neuronal survival

Marco Terenzio; Agostina Di Pizio; Ida Rishal; Letizia Marvaldi; Pierluigi Di Matteo; Riki Kawaguchi; Giovanni Coppola; Giampietro Schiavo; Elizabeth M.C. Fisher; Mike Fainzilber

Neurobiology of Disease (Jul 2020)

DYNLRB1 is essential for dynein mediated transport and neuronal survival

Marco Terenzio,
Agostina Di Pizio,
Ida Rishal,
Letizia Marvaldi,
Pierluigi Di Matteo,
Riki Kawaguchi,
Giovanni Coppola,
Giampietro Schiavo,
Elizabeth M.C. Fisher,
Mike Fainzilber

Affiliations

Marco Terenzio: 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; Corresponding author at: Molecular Neuroscience Unit, Okinawa Institute of Science and Technology Graduate University, Kunigami-gun, Okinawa 904-0412, Japan.
Agostina Di Pizio: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
Ida Rishal: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
Letizia Marvaldi: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
Pierluigi Di Matteo: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
Riki Kawaguchi: Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA
Giovanni Coppola: Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA
Giampietro Schiavo: 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
Elizabeth M.C. Fisher: Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK
Mike Fainzilber: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel

Journal volume & issue: Vol. 140
p. 104816

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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