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Title: Juvenile-onset loss of lipid-raft domains in attractin-deficient mice

Abstract

Mutations at the attractin (Atrn) locus in mice result in altered pigmentation on an agouti background, higher basal metabolic rate and juvenile-onset hypomyelination leading to neurodegeneration, while studies on human immune cells indicate a chemotaxis regulatory function. The underlying biochemical defect remains elusive. In this report we identify a role for attractin in plasma membrane maintenance. In attractin's absence there is a decline in plasma membrane glycolipid-enriched rafts from normal levels at 8 weeks to a complete absence by 24 weeks. The structural integrity of lipid rafts depends upon cholesterol and sphingomyelin, and can be identified by partitioning within of ganglioside GM{sub 1}. Despite a significant fall in cellular cholesterol with maturity, and a lesser fall in both membrane and total cellular GM{sub 1}, these parameters lag behind raft loss, and are normal when hypomyelination/neurodegeneration has already begun thus supporting consequence rather than cause. These findings can be recapitulated in Atrn-deficient cell lines propagated in vitro. Further, signal transduction through complex membrane receptor assemblies is not grossly disturbed despite the complete absence of lipid rafts. We find these results compatible with a role for attractin in plasma membrane maintenance and consistent with the proposal that the juvenile-onset hypomyelination and neurodegenerationmore » represent a defect in attractin-mediated raft-dependent myelin biogenesis.« less

Authors:
 [1];  [2];  [3]
  1. Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States)
  2. Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853 (United States)
  3. Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States). E-mail: Jonathan_Duke-Cohan@dfci.harvard.edu
Publication Date:
OSTI Identifier:
20972123
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 4; Other Information: DOI: 10.1016/j.yexcr.2006.11.018; PII: S0014-4827(06)00484-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CHOLESTEROL; IN VITRO; JUVENILES; MICE; MUTATIONS; MYELIN; RECEPTORS

Citation Formats

Azouz, Abdallah, Gunn, Teresa M., and Duke-Cohan, Jonathan S. Juvenile-onset loss of lipid-raft domains in attractin-deficient mice. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2006.11.018.
Azouz, Abdallah, Gunn, Teresa M., & Duke-Cohan, Jonathan S. Juvenile-onset loss of lipid-raft domains in attractin-deficient mice. United States. doi:10.1016/j.yexcr.2006.11.018.
Azouz, Abdallah, Gunn, Teresa M., and Duke-Cohan, Jonathan S. Thu . "Juvenile-onset loss of lipid-raft domains in attractin-deficient mice". United States. doi:10.1016/j.yexcr.2006.11.018.
@article{osti_20972123,
title = {Juvenile-onset loss of lipid-raft domains in attractin-deficient mice},
author = {Azouz, Abdallah and Gunn, Teresa M. and Duke-Cohan, Jonathan S.},
abstractNote = {Mutations at the attractin (Atrn) locus in mice result in altered pigmentation on an agouti background, higher basal metabolic rate and juvenile-onset hypomyelination leading to neurodegeneration, while studies on human immune cells indicate a chemotaxis regulatory function. The underlying biochemical defect remains elusive. In this report we identify a role for attractin in plasma membrane maintenance. In attractin's absence there is a decline in plasma membrane glycolipid-enriched rafts from normal levels at 8 weeks to a complete absence by 24 weeks. The structural integrity of lipid rafts depends upon cholesterol and sphingomyelin, and can be identified by partitioning within of ganglioside GM{sub 1}. Despite a significant fall in cellular cholesterol with maturity, and a lesser fall in both membrane and total cellular GM{sub 1}, these parameters lag behind raft loss, and are normal when hypomyelination/neurodegeneration has already begun thus supporting consequence rather than cause. These findings can be recapitulated in Atrn-deficient cell lines propagated in vitro. Further, signal transduction through complex membrane receptor assemblies is not grossly disturbed despite the complete absence of lipid rafts. We find these results compatible with a role for attractin in plasma membrane maintenance and consistent with the proposal that the juvenile-onset hypomyelination and neurodegeneration represent a defect in attractin-mediated raft-dependent myelin biogenesis.},
doi = {10.1016/j.yexcr.2006.11.018},
journal = {Experimental Cell Research},
number = 4,
volume = 313,
place = {United States},
year = {Thu Feb 15 00:00:00 EST 2007},
month = {Thu Feb 15 00:00:00 EST 2007}
}