EXPRESSION OF TRK RECEPTORS IN THE DEVELOPING AND ADULT HUMAN CENTRALAND PERIPHERAL NERVOUS-SYSTEM

A family of tyrosine receptor kinases known collectively as trk recept ors plays an essential role in signal transduction mediated by nerve g rowth factor and related neurotrophins. To localize the major trk rece ptors (trkA, B and C) in the developing and adult central (CNS) and pe ripheral (PNS) nervous system, we generated monoclonal antibodies (MAb s) to extracellular (MAbs E7, E13, E16, E21, E29) and intracellular (M Ab I2) domains of human trkA fused to glutathione S-transferase. Sever al MAbs (E7, E13, E16) recognized glycosylated trkA (gp140(trk) and gp 110(trk)) in Western blots, one MAb (E7) recognized non-glycosylated ( p80(trk)) and glycosylated trkA in immunoprecipitation assays, and two MAbs (E13, E29) detected trkA on the cell surface of NIH3T3 cells tra nsfected with a trkA cDNA. Although generated to trkA fusion proteins, this panel of MAbs also recognized trkB and trkC in flow cytometric s tudies of NIH3T3 cells transfected with trkB or trkC cDNAs. Thus, we u sed these pan-trk MAbs to probe selected regions of the CNS and PNS in cluding the hippocampus, nucleus basalis of Meynert, cerebellum, spina l cord, and dorsal root ganglion (DRG) to localize trkA, B, and C rece ptors in the developing and adult human nervous system. These studies showed that trk receptors are expressed primarily by neurons and are d etectable very early in the developing hippocampus, cerebellum, spinal cord, and DRG. Although the distribution and intensity of trk immunor eactivity changed with the progressive maturation of the CNS and PNS, immunoreactive trk receptors were detected in neurons of the adult hum an hippocampus, nucleus basalis of Meynert, cerebellum, spinal cord, a nd DRG. This first study of trk receptor proteins in the developing an d adult human CNS and PNS documents the expression of these receptors in subsets of neurons throughout the developing and adult nervous syst em. Thus, although the expression of trk receptor proteins is developm entally regulated, the constitutive expression of these neurotrophin r eceptors by neurons in many regions of the adult human CNS and PNS imp lies that mature trk receptor-bearing neurons retain the ability to re spond to neurotrophins long after terminal neuronal differentiation is complete. (C) 1995 Wiley-Liss, Inc.