EXPRESSION AND FUNCTION OF TRKB VARIANTS IN DEVELOPING SENSORY NEURONS

Mouse trigeminal neurons survive independently of neurotrophins when t heir axons are growing to their targets, and are then transiently supp orted by BDNF before becoming NGF dependent, During the stage of neuro trophin independence, transcripts encoding the BDNF receptor, TrkB, we re expressed at very low levels, During the stage of BDNF dependence, high levels of a transcript encoding a receptor with the catalytic tyr osine kinase domain were expressed, Although the levels of this transc ript fell as the neurons lost responsiveness to BDNF, there were conco mitant increases in the expression of transcripts encoding TrkB varian ts lacking the kinase domain, Analysis of RNA from purified neurons sh owed that all of these transcripts were present in neurons, BDNF and N GF up-regulated the expression of these transcripts early in developme nt but had little effect later on. To test whether truncated TrkB modu lates 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-expressio n of non-catalytic TrkB substantially reduced this response. Our resul ts suggest that BDNF responsiveness in sensory neurons during developm ent is modulated by the relative levels of catalytic and non-catalytic TrkB.