Expression and function of TrkB variants in developing sensory neurons.
Mouse trigeminal neurons survive independently of neurotrophins when their axons are growing to their targets, and are then transiently supported by BDNF before becoming NGF dependent. During the stage of neurotrophin independence, transcripts encoding the BDNF receptor, TrkB, were expressed at very low levels. During the stage of BDNF dependence, high levels of a transcript encoding a receptor with the catalytic tyrosine kinase domain were expressed. Although the levels of this transcript fell as the neurons lost responsiveness to BDNF, there were concomitant increases in the expression of transcripts encoding TrkB variants lacking the kinase domain. Analysis of RNA from purified neurons showed that all of these transcripts were present in neurons. BDNF and NGF up-regulated the expression of these transcripts early in development but had little effect later on. To test whether truncated TrkB modulates BDNF signalling via catalytic TrkB, we injected TrkB expression plasmids into NGF-dependent sympathetic neurons. Whereas expression of catalytic TrkB alone conferred a BDNF survival response, co-expression of non-catalytic TrkB substantially reduced this response. Our results suggest that BDNF responsiveness in sensory neurons during development is modulated by the relative levels of catalytic and non-catalytic TrkB.
Ninkina
N
N
School of Biological and Medical Sciences, University of St Andrews, UK.
Adu
J
J
Fischer
A
A
Piñón
L G
LG
Buchman
V L
VL
Davies
A M
AM
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D017931:DNA Primers; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D014158:Transcription, Genetic; D012668:Trigeminal Ganglion / Q000502:physiology*
D017931:DNA Primers; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases