title: Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR).
abstract: trkC receptors, which serve critical functions during the development of the nervous system, are alternatively spliced to yield isoforms containing the catalytic tyrosine kinase domain (TK+) and truncated isoforms which lack this domain (TK-). To test for potential differences in their roles during early stages of neural development, TK+ and TK- isoforms were ectopically expressed in cultures of neural crest, the stem cell population that gives rise to the vast majority of the peripheral nervous system. NT-3 activation of ectopically expressed trkC TK+ receptors promoted both proliferation of neural crest cells and neuronal differentiation. Strikingly, the trkC TK- isoform was significantly more effective at promoting neuronal differentiation, but had no effect on proliferation. Furthermore, the trkC TK- response was dependent on a conserved receptor cytoplasmic domain and required the participation of the p75(NTR) neurotrophin receptor. Antibody-mediated receptor dimerization of TK+ receptors, but not TK- receptors, was sufficient to stimulate differentiation. These data identify a phenotypic response to activation of the trkC TK- receptor and demonstrate a functional interaction with p75(NTR), indicating there may be multiple trkC receptor-mediated systems guiding neuronal differentiation.
authors.affiliation: Department of Biology, Montana State University, Bozeman, Montana 59717, Canada.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hapner
authors.forename: K L
authors.initials: KL
authors.lastname: Boeshore
authors.forename: T H
authors.initials: TH
authors.lastname: Large
authors.forename: F
authors.initials: F
authors.lastname: Lefcort
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation; D002642:Chick Embryo; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008958:Models, Molecular; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology; D009420:Nervous System / Q000166:cytology / Q000196:embryology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D020933:Neurotrophin 3; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D020800:Receptor, Nerve Growth Factor; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC