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Reduced N-Acetylaspartate Levels in Mice Lacking Aralar, a Brain- and Muscle-type Mitochondrial Aspartate-glutamate Carrier.
- Source :
-
Journal of Biological Chemistry . 9/2/2005, Vol. 280 Issue 35, p31333-31339. 7p. 1 Black and White Photograph, 5 Graphs. - Publication Year :
- 2005
-
Abstract
- Aralar is a mitochondrial calcium-regulated aspartate-glutamate carrier mainly distributed in brain and skeletal muscle, involved in the transport of aspartate from mitochondria to cytosol, and in the transfer of cytosolic reducing equivalents into mitochondria as a member of the malate-aspartate NADH shuttle. In the present study, we describe the characteristics of aralar-deficient (Aralar-/-) mice, generated by a gene-trap method, showing no aralar mRNA and protein, and no detectable malate-aspartate shuttle activity in skeletal muscle and brain mitochondria. Aralar-/- mice were growth-retarded, exhibited generalized tremoring, and had pronounced motor coordination defects along with an impaired myelination in the central nervous system. Analysis of lipid components showed a marked decrease in the myelin lipid galactosyl cerebroside. The content of the myelin lipid precursor, N-acetylaspartate, and that of aspartate are drastically decreased in the brain of Aralar-/- mice. The defect in N-acetylaspartate production was also observed in cell extracts from primary neuronal cultures derived from Aralar-/- mouse embryos. These results show that aralar plays an important role in myelin formation by providing aspartate for the synthesis of N-acetylaspartate in neuronal cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MITOCHONDRIA
*CYTOSOL
*ASPARTIC acid
*MESSENGER RNA
*PROTEINS
*LABORATORY mice
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 280
- Issue :
- 35
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18352951
- Full Text :
- https://doi.org/10.1074/jbc.M505286200