Neural differentiation promoted by truncated trkC receptors in collaboration with p75NTR

被引:71
作者
Hapner, SJ
Boeshore, KL
Large, TH
Lefcort, F [1 ]
机构
[1] Montana State Univ, Dept Biol, Bozeman, MT 59717 USA
[2] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA
[3] Sphinx Pharmaceut, Durham, NC 27707 USA
关键词
D O I
10.1006/dbio.1998.8970
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (C) 1998 Academic Press.
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页码:90 / 100
页数:11
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