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Originally published In Press as doi:10.1074/jbc.M005214200 on July 5, 2000

J. Biol. Chem., Vol. 275, Issue 39, 30537-30545, September 29, 2000
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Chopper, a New Death Domain of the p75 Neurotrophin Receptor That Mediates Rapid Neuronal Cell Death*

Elizabeth J. CoulsonDagger , Kate Reid, Manuel Baca, Kylie A. Shipham, Sarah M. Hulett, Trevor J. Kilpatrick, and Perry F. Bartlett

From the Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia

The cytoplasmic juxtamembrane region of the p75 neurotrophin receptor (p75NTR) has been found to be necessary and sufficient to initiate neural cell death. The region was named "Chopper" to distinguish it from CD95-like death domains. A 29-amino acid peptide corresponding to the Chopper region induced caspase- and calpain-mediated death in a variety of neural and non-neural cell types and was not inhibited by signaling through Trk (unlike killing by full-length p75NTR). Chopper triggered cell death only when bound to the plasma membrane by a lipid anchor, whereas non-anchored Chopper acted in a dominant-negative manner, blocking p75NTR-mediated death both in vitro and in vivo. Removal of the ectodomain of p75NTR increased the potency of Chopper activity, suggesting that it regulates the association of Chopper with downstream signaling proteins.

* This work was supported by the National Health and Medical Research Council of Australia, the Motor Neuron Disease Association of Australia, and Parkinson's Victoria Inc.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed. Tel.: 61-3-9345-2538; Fax: 61-3-9347-0852; E-mail: coulson@wehi.edu.au.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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