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Specific downregulation and mistargeting of the lipid raft-associated protein MAL in a glycolipid storage disorder

Saravanan, K. and Schaeren-Wiemers, N. and Klein, D. and Sandhoff, R. and Schwarz, A. and Yaghootfam, A. and Gieselmann, V. and Franken, S.. (2004) Specific downregulation and mistargeting of the lipid raft-associated protein MAL in a glycolipid storage disorder. Neurobiology of disease, Vol. 16, no. 2. pp. 396-406.

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Official URL: http://edoc.unibas.ch/dok/A5838865

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Abstract

Metachromatic leukodystrophy (MLD) is a lysosomal lipid storage disease caused by arylsulfatase A deficiency. In MLD patients the sphingolipid sulfatide increasingly accumulates leading to progressive demyelination. We have analysed arylsulfatase A-deficient mice, a MLD mouse model, and we show that accumulation of sulfatide is not restricted to the lysosomal compartment but also occurs in myelin itself. Although, this sulfatide storage did not affect the overall composition of most myelin proteins, it specifically caused a severe reduction of MAL. This demonstrates a regulatory link between sulfatide accumulation and MAL expression and indicates the existence of regulatory mechanisms between lipid and myelin protein synthesis in oligodendrocytes. In addition, in cultured renal epithelial cells, sulfatide accumulation diverts MAL to the late endosomal/lysosomal compartment and thus also affects the intracellular distribution of MAL. The specific reduction and mistargeting of MAL protein as a reaction to sulfatide overload may contribute to the pathogenic mechanisms in metachromatic leukodystrophy.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neurobiology (Schaeren-Wiemers)
UniBasel Contributors:Schaeren-Wiemers, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0969-9961
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:26 Apr 2013 07:02
Deposited On:26 Apr 2013 06:57

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