NDLI: Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies.

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Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yi, H. Gutekunst, C. A. Rees, H. D. Levey, A. I. Hersch, S. M. Whaley, W. L. Nash, N. R. Heilman, C. J. Madden, J. J.
Description	Author Affiliation: Gutekunst CA ( Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.);
Abstract	The Huntington disease (HD) phenotype is associated with expansion of a trinucleotide repeat in the IT15 gene, which is predicted to encode a 348-kDa protein named huntington. We used polyclonal and monoclonal anti-fusion protein antibodies to identify native huntingtin in rat, monkey, and human. Western blots revealed a protein with the expected molecular weight which is present in the soluble fraction of rat and monkey brain tissues and lymphoblastoid cells from control cases. In lymphoblastoid cell lines from juvenile-onset heterozygote HD cases, both normal and mutant huntingtin are expressed, and increasing repeat expansion leads to lower levels of the mutant protein. Immunocytochemistry indicates that huntingtin is located in neurons throughout the brain, with the highest levels evident in larger neurons. In the human striatum, huntingtin is enriched in a patch-like distribution, potentially corresponding to the first areas affected in HD. Subcellular localization of huntingtin is consistent with a cytosolic protein primarily found in somatodendritic regions. Huntingtin appears to particularly associate with microtubules, although some is also associated with synaptic vesicles. On the basis of the localization of huntingtin in association with microtubules, we speculate that the mutation impairs the cytoskeletal anchoring or transport of mitochondria, vesicles, or other organelles or molecules.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	92
Language	English
Publisher	National Academy of Sciences
Publisher Date	1995-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Chemistry Hematopoietic Stem Cells Chemistry Huntington Disease Lymphocytes Nerve Tissue Proteins Isolation & Purification Nuclear Proteins Animals Brain Cytology Cell Compartmentation Cell Line Cytosol Haplorhini Immunohistochemistry Microscopy, Immunoelectron Immunology Neurons Recombinant Fusion Proteins Tissue Distribution Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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