Expression of Mutant Huntingtin Blocks Exocytosis in PC12 Cells by Depletion of Complexin II

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. We reported recently that complexin II, a protein involved in neurotransmitter release, is depleted from both the brains of mice carrying the HD mutation and from the s...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-08, Vol.278 (33), p.30849-30853
Main Authors: Edwardson, J.Michael, Wang, Chih-Tien, Gong, Belvin, Wyttenbach, Andreas, Bai, Jihong, Jackson, Meyer B., Chapman, Edwin R., Morton, A.Jennifer
Format: Article
Language:English
Subjects:
Adaptor Proteins, Vesicular Transport
Animals
Calcium - metabolism
Exocytosis - physiology
Humans
Huntingtin Protein
Mice
Mice, Transgenic
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurons - cytology
Neurons - metabolism
Neurotransmitter Agents - metabolism
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
PC12 Cells
Rats
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Summary:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. We reported recently that complexin II, a protein involved in neurotransmitter release, is depleted from both the brains of mice carrying the HD mutation and from the striatum of post mortem HD brains. Here we show that this loss of complexin II is recapitulated in PC12 cells expressing the HD mutation and is accompanied by a dramatic decline in Ca2+-triggered exocytosis of neurotransmitter. Overexpression of complexin II (but not complexin I) rescued exocytosis, demonstrating that the decline in neurotransmitter release is a direct consequence of complexin II depletion. Complexin II depletion in the brain may account for some of the abnormalities in neurotransmission associated with HD.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M304615200