Early evolutionary origin of the neurotrophin receptor family.
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.
van Kesteren
R E
RE
Graduate School of Neurosciences Amsterdam, Research Institute Neurosciences, Vrije Universiteit, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands. revankes@bio.vu.nl
Fainzilber
M
M
Hauser
G
G
van Minnen
J
J
Vreugdenhil
E
E
Smit
A B
AB
Ibáñez
C F
CF
Geraerts
W P
WP
Bulloch
A G
AG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D006801:Humans; D007448:Invertebrates; D008195:Lymnaea / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism; D020933:Neurotrophin 3; D010802:Phylogeny; D011487:Protein Conformation; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection; D014714:Vertebrates
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D020794:Receptor Protein-Tyrosine Kinases