Skip Navigation


Human Molecular Genetics Advance Access originally published online on September 14, 2004
Human Molecular Genetics 2004 13(21):2581-2594; doi:10.1093/hmg/ddh291
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
13/21/2581    most recent
ddh291v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (11)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Teijido, O.
Right arrow Articles by Estévez, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Teijido, O.
Right arrow Articles by Estévez, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol. 13, No. 21 © Oxford University Press 2004; all rights reserved

Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts

Oscar Teijido1, Albert Martínez2, Michael Pusch3, Antonio Zorzano1, Eduardo Soriano2, Jose Antonio del Río2, Manuel Palacín1 and Raúl Estévez1,*

1Department of Biochemistry and Molecular Biology and 2Department of Cell Biology, Faculty of Biology and Barcelona Science Park, Josep Samitier 1-5. Barcelona E-08028, Spain and 3Istituto di Biofisica, Via de Marini 6, I-16149 Genova, Italy

Received July 1, 2004; Accepted September 6, 2004

Mutations in the MLC1 gene are responsible for one form of the neurological disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC). The disease is a type of vacuolating myelinopathy. The biochemical properties and the function of the MLC1 protein are unknown. To characterize MLC1, we generated polyclonal antibodies. The MLC1 protein was detected in the brain, assembled into higher molecular complexes, as assessed by assembly-dependent trafficking assays. In situ hybridization and immunohistochemistry were used to determine MLC1 localization within the adult mouse brain. MLC1 was expressed in neurons, detected preferentially in particular axonal tracts. This expression pattern correlates with the major phenotype observed in the disease. In addition, it was expressed in some astrocytes, concentrating in Bergmann glia, the astrocyte end-feet membranes adjacent to blood vessels and in astrocyte–astrocyte membrane contact regions. Other neuronal barriers, such as the ependyma and the pia mater, were also positive for MLC1 expression. MLC1 was detected in vivo and in heterologous systems at the plasma membrane. MLC mutations impaired folding, and the defect was corrected in vitro by addition of curcumin, a Ca2+-ATPase inhibitor. In summary, this study provides an explanation as to why mutations in MLC1 provoke the disease and points to a possible therapy for some patients.

* To whom correspondence should be addressed. Tel: +34 934034700; Fax: +34 934034717; Email: restevez{at}pcb.ub.es


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
A. Duarri, O. Teijido, T. Lopez-Hernandez, G. C. Scheper, H. Barriere, I. Boor, F. Aguado, A. Zorzano, M. Palacin, A. Martinez, et al.
Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects
Hum. Mol. Genet., December 1, 2008; 17(23): 3728 - 3739.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.