The Trk family of neurotrophin receptors

Abstract

Accumulating evidence indicates that the Trk family of tyrosine protein kinase receptors, Trk (also known as TrkA), TrkB, and TrkC, are responsible for mediating the trophic effects of the NGF family of neurotrophins. Nerve growth factor (NGF) specifically recognizes Trk, a receptor indentified in all major NGF targets, including sympathetic, trigeminal, and dorsal root ganglia as well as in cholinergic neurons of the basal forebrain and the striatum. Brain‐derived neurotropic factor (BDNF) and neurotrophin‐4 (NT‐4) specifically activate the TrkB tyrosine kinase receptor. trk B transcripts encoding this receptor are found throughout multiple structure of the central and peripheral nervous system. Neurotrophin‐3 (NT‐3) primarily activates the TrkC tyrosine protein kinases, four related isoforns encoded by alternative splicing of trk C, a gene also wildely expressed throughtout the mammalian nervous system. Unlike the other neurotrophins, NT‐3 appears to be somewhat promiscuous since it can activate Trk and TrkB kinase receptors, at least in certain cell systems. The trk B and trkC genes also encode noncatalytic neurotrophin receptor isoforms of an as yet, unknown function. Recently, strains of mice lacking each of these tyrosine kinase receptors have been generated. Preliminary characterization of these mutant mice has provided significant information regarding the role of these receptors in the ontogeny of the mammlian nervous system. For instance, mice deficient for Trk receptors lack most sympathetic neurons and do not display nociceptive and temperature sensations, two defects likely to result from severe neuronal cell loss in their trigeminal and dorsal root ganglia. Mice lacking TrkB tyrosine kinase receptors die postnatally due to their inability to intake food. Neuron cell loss in their trigeminal, nodose and pretrosal sensory ganglia as well as in the facial motor nucleus are likely to contribute to this phenotype. Finally, TrkC‐deficient mice display strikingly abnormal movements consistent with loss of proprioception, a defect likely to be a consequence of the complete loss of Ia muscle afferents observed in this mutant mice. 1994 John Wiley & Sons, Inc.