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Expression of trk receptors in the developing and adult human central and peripheral nervous system
Author(s) -
Muragaki Yoshihiro,
Timothy Nigel,
Leight Susan,
Hempstead Barbara L.,
Chao Moses V.,
Trojanowski John Q.,
Lee Virginia M.Y.
Publication year - 1995
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.903560306
Subject(s) - trk receptor , biology , neurotrophin , receptor , tropomyosin receptor kinase a , microbiology and biotechnology , neuroscience , biochemistry
A family of tyrosine receptor kinases known collectively as trk receptors plays an essential role in signal transduction mediated by nerve growth factor and related neurotrophins. To localize the major trk receptors ( trk A, B and C) in the developing and adult central (CNS) and peripheral (PNS) nervous system, we generated monoclonal antibodies (MAbs) to extracellular (MAbs E7, E13, E16, E21, E29) and intracellular (MAb I2) domains of human trk A fused to glutathione S‐transferase. Several MAbs (E7, E13, E16) recognized glycosylated trk A (gp 140 trk and gp110 trk ) in Western blots, one MAb (E7) recognized non‐glycosylated (p80 trk ) and glycosylated trk A in immunoprecipitation assays, and two MAbs (E13, E29) detected trk A on the cell surface of NIH3T3 cells transfected with a trk A cDNA. Although generated to trk A fusion proteins, this panel of MAbs also recognized trk B and trk C in flow cytometric studies of NIH3T3 cells transfected with trk B or trk C cDNAs. Thus, we used these pan‐ trk MAbs to probe selected regions of the CNS and PNS including the hippocampus, nucleus basalis of Meynert, cerebellum, spinal cord, and dorsal root ganglion (DRG) to localize trk A, B, and C receptors in the developing and adult human nervous system. These studies showed that trk receptors are expressed primarily by neurons and are detectable very early in the developing hippocampus, cerebellum, spinal cord, and DRG. Although the distribution and intensity of trk immunoreactivity changed with the progressive maturation of the CNS and PNS, immunoreactive trk receptors were detected in neurons of the adult human hippocampus, nucleus basalis of Meynert, cerebellum, spinal cord, and DRG. This first study of trk receptor proteins in the developing and adult human CNS and PNS documents the expression of these receptors in subsets of neurons throughout the developing and adult nervous system. Thus, although the expression of trk receptor proteins is developmentally regulated, the constitutive expression of these neurotrophin receptors by neurons in many regions of the adult human CNS and PNS implies that mature trk receptor‐bearing neurons retain the ability to respond to neurotrophins long after terminal neuronal differentiation is complete. © 1995 Wiley‐Liss, Inc.