NEUROTROPHIN-4 - THE ODD ONE OUT IN THE NEUROTROPHIN FAMILY

Neurotrophin-4 (NT-4) is a member of a family of neurotrophic factors, the neurotrophins, that control survival and differentiation of verte brate neurons (2-4). Besides being the most recently discovered neurot rophin in mammals, and the least well understood, several aspects dist inguish NT-4 from other members of the neurotrophin family. It is the most divergent member and, in contrast to the other neurotrophins, its expression is ubiquitous and appears to be less influenced by environ mental signals. NT-4 seems to have the unique requirement of binding t o the low-affinity neurotrophin receptor (p75(LNGFR)) for efficient si gnalling and retrograde transport in neurons. Moreover, while all othe r neurotrophin knock-outs have proven lethal during early postnatal de velopment, mice deficient in NT-4 have so far only shown minor cellula r deficits and develop normally to adulthood. Is NT-4 a recent additio n to the neurotrophic factor repertoire in search of a crucial functio n, or is it an evolutionary relic, a kind of wisdom tooth of the neuro trophin family?