title: Transmembrane semaphorin5B is proteolytically processed into a repulsive neural guidance cue.
abstract: Developing neuronal growth cones respond to a number of post-transcriptionally modified guidance cues to establish functional neural networks. The Semaphorin family has well-established roles as both secreted and transmembrane guidance cues. Here, we describe the first evidence that a transmembrane Semaphorin, Semaphorin 5B (Sema5B), is proteolytically processed from its transmembrane form and can function as a soluble growth cone collapsing guidance cue. Over-expression of A Disintegrin and Metalloprotease (ADAM)-17, results in an enhanced release of the Sema5B ectodomain, while removal of a predicted ADAM-17 cleavage site prevents its release. In contrast, knockdown of ADAM-17 does not significantly reduce Sema5B release, indicating there are additional unknown compensating proteases. This modulation of the transmembrane Sema5B to a diffusible cue represents a sophisticated method to regulate neuronal guidance in vivo.
authors: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Kristen
authors: K
authors: Browne
authors: Wenyan
authors: W
authors: Wang
authors: Rachel Q
authors: RQ
authors: Liu
authors: Matthew
authors: M
authors: Piva
authors: Timothy P
authors: TP
authors: O'Connor
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement; D002642:Chick Embryo; D002645:Chickens; D018920:Coculture Techniques; D019281:Dimerization; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009924:Organ Culture Techniques; D011480:Protease Inhibitors / Q000494:pharmacology; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
chemical_list: D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D009419:Nerve Tissue Proteins; D011480:Protease Inhibitors; D039961:Semaphorins; D019715:Tissue Inhibitor of Metalloproteinase-1; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human