DYNLRB1 is essential for dynein mediated transport and neuronal survival
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 s...
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doaj-a7f68d6d22dc48f092bfe14b419df4362021-03-22T08:41:41ZengElsevierNeurobiology of Disease1095-953X2020-07-01140104816DYNLRB1 is essential for dynein mediated transport and neuronal survivalMarco Terenzio0Agostina Di Pizio1Ida Rishal2Letizia Marvaldi3Pierluigi Di Matteo4Riki Kawaguchi5Giovanni Coppola6Giampietro Schiavo7Elizabeth M.C. Fisher8Mike Fainzilber9Department 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.Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USADepartments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USADepartment 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, UKDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UKDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, IsraelThe 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.http://www.sciencedirect.com/science/article/pii/S0969996120300917dynlrb1Dynein complexAxonal transportNeuronal survivalNeurodegeneration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marco Terenzio Agostina Di Pizio Ida Rishal Letizia Marvaldi Pierluigi Di Matteo Riki Kawaguchi Giovanni Coppola Giampietro Schiavo Elizabeth M.C. Fisher Mike Fainzilber |
spellingShingle |
Marco Terenzio Agostina Di Pizio Ida Rishal Letizia Marvaldi Pierluigi Di Matteo Riki Kawaguchi Giovanni Coppola Giampietro Schiavo Elizabeth M.C. Fisher Mike Fainzilber DYNLRB1 is essential for dynein mediated transport and neuronal survival Neurobiology of Disease dynlrb1 Dynein complex Axonal transport Neuronal survival Neurodegeneration |
author_facet |
Marco Terenzio Agostina Di Pizio Ida Rishal Letizia Marvaldi Pierluigi Di Matteo Riki Kawaguchi Giovanni Coppola Giampietro Schiavo Elizabeth M.C. Fisher Mike Fainzilber |
author_sort |
Marco Terenzio |
title |
DYNLRB1 is essential for dynein mediated transport and neuronal survival |
title_short |
DYNLRB1 is essential for dynein mediated transport and neuronal survival |
title_full |
DYNLRB1 is essential for dynein mediated transport and neuronal survival |
title_fullStr |
DYNLRB1 is essential for dynein mediated transport and neuronal survival |
title_full_unstemmed |
DYNLRB1 is essential for dynein mediated transport and neuronal survival |
title_sort |
dynlrb1 is essential for dynein mediated transport and neuronal survival |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2020-07-01 |
description |
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. |
topic |
dynlrb1 Dynein complex Axonal transport Neuronal survival Neurodegeneration |
url |
http://www.sciencedirect.com/science/article/pii/S0969996120300917 |
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