title: The chemorepulsive activity of the axonal guidance signal semaphorin D requires dimerization.
abstract: The axonal guidance signal semaphorin D is a member of a large family of proteins characterized by the presence of a highly conserved semaphorin domain of about 500 amino acids. The vertebrate semaphorins can be divided into four different classes that contain both secreted and membrane-bound proteins. Here we show that class III (SemD) and class IV semaphorins (SemB) form homodimers linked by intermolecular disulfide bridges. In addition to the 95-kDa form of SemD (SemD(95k)), proteolytic processing of SemD creates a 65-kDa isoform (SemD(65k)) that lacks the 33-kDa carboxyl-terminal domain. Although SemD(95k) formed dimers, the removal of the carboxyl-terminal domain resulted in the dissociation of SemD homodimers to monomeric SemD(65k). Mutation of cysteine 723, one of four conserved cysteine residues in the 33-kDa fragment, revealed its requirement both for the dimerization of SemD and its chemorepulsive activity. We suggest that dimerization is a general feature of sema- phorins which depends on class-specific sequences and is important for their function.
authors.affiliation: Molekulare Neurogenetik, Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Deutschordenstrasse 46, D-60528 Frankfurt/Main, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Klostermann
authors.forename: M
authors.initials: M
authors.lastname: Lohrum
authors.forename: R H
authors.initials: RH
authors.lastname: Adams
authors.forename: A W
authors.initials: AW
authors.lastname: Püschel
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D019281:Dimerization; D018604:Epitope Mapping; D006023:Glycoproteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D040121:Semaphorin-3A; D013329:Structure-Activity Relationship
chemical_list: D006023:Glycoproteins; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D040121:Semaphorin-3A