Collapsin-1 Covalently Dimerizes, and Dimerization Is Necessary for Collapsing Activity*
- From the Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Abstract
Chick collapsin-1, the first identified vertebrate member of the semaphorin family of axon guidance proteins, repels specific growth cones. Like all family members, collapsin-1 contains within its sequence a semaphorin domain that is necessary for specifying activity. Two additional structural domains of collapsin-1, the immunoglobulin (Ig) domain and the basic tail, each potentiate collapsin-1 activity. We identify in this study another structural feature of collapsin-1 that is necessary for its function. Collapsin-1 covalently dimerizes, and dimerization is necessary for collapse activity. This dimerization is mediated through a cysteine at residue 723, between the Ig domain and basic tail. The semaphorin domain alone is not active since it cannot dimerize. The collapsing activity of the semaphorin domain can be reconstituted when made as a chimeric construct with an immunoglobin Fc domain, which promotes dimerization.
Footnotes
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↵* This work was supported by a University of Pennsylvania Medical Scientist Training Program grant (to A. M. K.) and by grants (to J. A. R.) from the National Institutes of Health and the McKnight Foundation.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.
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↵‡ To whom correspondence should be addressed. Tel.: 215-898-2180; Fax: 215-573-9050; E-mail: raperj{at}mail.med.upenn.edu.
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↵1 The abbreviations used are: DRG, dorsal root ganglia; PCR, polymerase chain reaction; HPLC, high performance liquid chromatography; PDGF, platelet-derived growth factor; VPF, vascular permeability factor; VEGF, vascular endothelial growth factor.
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- Received September 29, 1997.
- Revision received March 13, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
