Intracellular transport of the DM-20 bearing shaking pup (shp) mutation and its possible phenotypic consequences.

Details

Serval ID
serval:BIB_1462
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intracellular transport of the DM-20 bearing shaking pup (shp) mutation and its possible phenotypic consequences.
Journal
Journal of Neuroscience Research
Author(s)
Tosic M., Matthey B., Gow A., Lazzarini R.A., Matthieu J.M.
ISSN
0360-4012
Publication state
Published
Issued date
1997
Volume
50
Number
5
Pages
844-852
Language
english
Notes
Publication types: Journal Article
Abstract
Paralytic tremor (pt) in rabbits and shaking pup (shp) in dogs are allelic dysmyelinated mutants of the proteolipid protein (Plp) gene. Both mutations affect the same amino acid, histidine36, which is replaced by glutamine in pt and by proline in shp. Phenotypic expression of these two mutations is very different. Paralytic tremor presents a much milder form of dysmyelination than shaking pup. The number of oligodendrocytes in the mutant rabbit is normal, while in the dog, the oligodendrocyte number is reduced due to early death or incomplete maturation. We have previously reported an abnormal intracellular transport of the PLPpt, whereas DM-20pt was normally transported to the cell membrane. In the present study, we show that the transport of the two isoforms containing the shp mutation is impaired in transfected Cos-7 cells. Cotransfecting cells with different ratios and combinations of mutated PLP and DM-20 cDNAs, we demonstrated that DM-20pt, but not DM-20shp, facilitates intracellular trafficking and integration into the plasma membrane of either of the two mutated PLPs. The phenotypic difference between these two allelic mutations can result from differences in DM-20 protein trafficking and sorting. These results show that the loss of function of PLP is not position-dependent but depends on the nature of the mutation.
Keywords
Animals, COS Cells, Cell Membrane/metabolism, Demyelinating Diseases/genetics, Demyelinating Diseases/veterinary, Dog Diseases, Dogs, Myelin Proteolipid Protein/biosynthesis, Myelin Proteolipid Protein/genetics, Nerve Tissue Proteins, Paralysis/genetics, Paralysis/veterinary, Phenotype, Rabbits, Rats, Recombinant Proteins/biosynthesis, Transfection, Tremor/genetics, Tremor/veterinary
Pubmed
Web of science
Create date
19/11/2007 12:07
Last modification date
20/08/2019 12:43
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