skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope protein in sensory neurons

Abstract

Dystonin/Bpag1 proteins are cytoskeletal linkers whose loss of function in mice results in a hereditary sensory neuropathy with a progressive loss of limb coordination starting in the second week of life. These mice, named dystonia musculorum (dt), succumb to the disease and die of unknown causes prior to sexual maturity. Previous evidence indicated that cytoskeletal defects in the axon are a primary cause of dt neurodegeneration. However, more recent data suggests that other factors may be equally important contributors to the disease process. In the present study, we demonstrate perikaryal defects in dorsal root ganglion (DRG) neurons at stages preceding the onset of loss of limb coordination in dt mice. Abnormalities include alterations in endoplasmic reticulum (ER) chaperone protein expression, indicative of an ER stress response. Dystonin in sensory neurons localized in association with the ER and nuclear envelope (NE). A fusion protein ofthe dystonin-a2 isoform, which harbors an N-terminal transmembrane domain, associated with and reorganized the ER in cell culture. This isoform also interacts with the NE protein nesprin-3{alpha}, but not nesprin-3{beta}. Defects in dt mice, as demonstrated here, may ultimately result in pathogenesis involving ER dysfunction and contribute significantly to the dt phenotype.

Authors:
 [1];  [1]
  1. Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6 (Canada)
Publication Date:
OSTI Identifier:
21128152
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 314; Journal Issue: 15; Other Information: DOI: 10.1016/j.yexcr.2008.06.021; PII: S0014-4827(08)00251-6; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; CELL CULTURES; ENDOPLASMIC RETICULUM; GANGLIONS; LIMBS; MICE; NERVE CELLS; PATHOGENESIS; PHENOTYPE

Citation Formats

Young, Kevin G, University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Kothary, Rashmi, University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, and Department of Medicine, University of Ottawa, Ottawa, Ontario. Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope protein in sensory neurons. United States: N. p., 2008. Web. doi:10.1016/j.yexcr.2008.06.021.
Young, Kevin G, University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Kothary, Rashmi, University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, & Department of Medicine, University of Ottawa, Ottawa, Ontario. Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope protein in sensory neurons. United States. https://doi.org/10.1016/j.yexcr.2008.06.021
Young, Kevin G, University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Kothary, Rashmi, University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, and Department of Medicine, University of Ottawa, Ottawa, Ontario. 2008. "Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope protein in sensory neurons". United States. https://doi.org/10.1016/j.yexcr.2008.06.021.
@article{osti_21128152,
title = {Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope protein in sensory neurons},
author = {Young, Kevin G and University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario and Kothary, Rashmi and University of Ottawa Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario and Department of Medicine, University of Ottawa, Ottawa, Ontario},
abstractNote = {Dystonin/Bpag1 proteins are cytoskeletal linkers whose loss of function in mice results in a hereditary sensory neuropathy with a progressive loss of limb coordination starting in the second week of life. These mice, named dystonia musculorum (dt), succumb to the disease and die of unknown causes prior to sexual maturity. Previous evidence indicated that cytoskeletal defects in the axon are a primary cause of dt neurodegeneration. However, more recent data suggests that other factors may be equally important contributors to the disease process. In the present study, we demonstrate perikaryal defects in dorsal root ganglion (DRG) neurons at stages preceding the onset of loss of limb coordination in dt mice. Abnormalities include alterations in endoplasmic reticulum (ER) chaperone protein expression, indicative of an ER stress response. Dystonin in sensory neurons localized in association with the ER and nuclear envelope (NE). A fusion protein ofthe dystonin-a2 isoform, which harbors an N-terminal transmembrane domain, associated with and reorganized the ER in cell culture. This isoform also interacts with the NE protein nesprin-3{alpha}, but not nesprin-3{beta}. Defects in dt mice, as demonstrated here, may ultimately result in pathogenesis involving ER dysfunction and contribute significantly to the dt phenotype.},
doi = {10.1016/j.yexcr.2008.06.021},
url = {https://www.osti.gov/biblio/21128152}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 15,
volume = 314,
place = {United States},
year = {Wed Sep 10 00:00:00 EDT 2008},
month = {Wed Sep 10 00:00:00 EDT 2008}
}