Early evolutionary origin of the neurotrophin receptor family

R.E. van Kesteren, M. Fainzilber, G. Hauser, J. van Minnen, E. Vreugdenhil, A.B. Smit, C.F. Ibanez, W.P.M. Geraerts, A.G.M. Bulloch

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Neurotrophins and their Trk receptors play a crucial role in the development and maintenance of the vertebrate nervous system, but to date no component of this signalling system has been found in invertebrates. We describe a molluscan Trk receptor, designated Ltrk, from the snail Lymnaea stagnalis. The full-length sequence of Ltrk reveals most of the characteristics typical of Trk receptors, including highly conserved transmembrane and intracellular tyrosine kinase domains, and a typical extracellular domain of leucine-rich motifs flanked by cysteine clusters. In addition, Ltrk has a unique N-terminal extension and lacks immunoglobulin-like domains. Ltrk is expressed during development in a stage-specific manner, and also in the adult, where its expression is confined to the central nervous system and its associated endocrine tissues. Ltrk has the highest sequence identity with the TrkC mammalian receptor and, when exogenously expressed in fibroblasts or COS cells, binds human NT-3, but not NGF or BDNF, with an affinity of 2.5 nM. These findings support an early evolutionary origin of the Trk family as neuronal receptor tyrosine kinases and suggest that Trk signalling mechanisms may be highly conserved between vertebrates and invertebrates.
Original languageEnglish
Pages (from-to)2534-2542
Number of pages9
JournalEMBO Journal
Volume17
DOIs
Publication statusPublished - 1998

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