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Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of complexin II

Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of complexin II
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 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.
0021-9258
30849-30853
Edwardson, J.M.
014e633d-8e59-4577-9295-c52896b71727
Wang, C.T.
09b0cb82-e411-4ec1-b2a5-3377b26fe37f
Gong, B.
112d9ffc-1cdc-447b-a665-b8006c520c93
Wyttenbach, A.
69846a0f-fb60-4a28-84eb-ed865a5e31fa
Bai, J.H.
9e4fb9ea-8a78-4389-82d9-163ea4ce43ba
Jackson, M.B.
8bbdf289-2191-44cf-a361-037f8ea88bbc
Chapman, E.R.
4f755fd8-b238-420d-8cdd-deb6ae70b152
Morton, A.J.
d393fa4d-c9bd-45e6-9265-c912814a2703
Edwardson, J.M.
014e633d-8e59-4577-9295-c52896b71727
Wang, C.T.
09b0cb82-e411-4ec1-b2a5-3377b26fe37f
Gong, B.
112d9ffc-1cdc-447b-a665-b8006c520c93
Wyttenbach, A.
69846a0f-fb60-4a28-84eb-ed865a5e31fa
Bai, J.H.
9e4fb9ea-8a78-4389-82d9-163ea4ce43ba
Jackson, M.B.
8bbdf289-2191-44cf-a361-037f8ea88bbc
Chapman, E.R.
4f755fd8-b238-420d-8cdd-deb6ae70b152
Morton, A.J.
d393fa4d-c9bd-45e6-9265-c912814a2703

Edwardson, J.M., Wang, C.T., Gong, B., Wyttenbach, A., Bai, J.H., Jackson, M.B., Chapman, E.R. and Morton, A.J. (2003) Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of complexin II. The Journal of Biological Chemistry, 278 (33), 30849-30853. (doi:10.1074/jbc.M304615200).

Record type: Article

Abstract

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.

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Published date: 1 August 2003

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Local EPrints ID: 56521
URI: http://eprints.soton.ac.uk/id/eprint/56521
ISSN: 0021-9258
PURE UUID: 2076b8f9-b2bd-4767-bce6-cbbff1c13fa7

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Date deposited: 07 Aug 2008
Last modified: 15 Mar 2024 11:02

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Author: J.M. Edwardson
Author: C.T. Wang
Author: B. Gong
Author: A. Wyttenbach
Author: J.H. Bai
Author: M.B. Jackson
Author: E.R. Chapman
Author: A.J. Morton

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