[Mutations in structural genes of tryptophan metabolic enzymes of the kynurenine pathway modulate some units of the L-glutamate receptor--actin cytoskeleton signaling cascade].
Methods of immunohistochemistry and fluorescent staining was used to study the localization and amounts of protein components of the signal cascade connecting the receptor link (NMDA-subtype glutamate receptor) with actin of the cytoskeleton in the head ganglia of Drosophila strain Canton-S (wild type, control) and strains carrying mutations vermilion, cinnabar, and cardinal, which sequentially inactivate tryptophan-hydrolyzing enzymes during its metabolism into ommochrome. The obtained data are evidence for modulatory effects of genes controlling the kynurenine pathway of tryptophan metabolism on the major components of the signal cascade: the initial link (NMDA receptor, postsynaptic density protein-95, a structural protein involved in receptor localization and internalization), the intermediate link (limkinase-l, the key neuronal enzyme in actin remodeling) and the final link (f-actin, the critical factor in the morphogenesis of synaptic structures and, hence, in the processes of synaptic plasticity, learning and memory). It is suggested that kynurenine acid (an endogenous nonspecific antagonist of L-glutamate receptor) and 3-hydroxykynurenine capable of inducing a nonspecific stimulating effect are biochemical intermediates of the effects of these genes.
Lopatina
N G
NG
Zachepilo
T G
TG
Chesnokova
E G
EG
Savateeva-Popova
E V
EV
D000199:Actins / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins / Q000032:analysis / Q000235:genetics*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D005136:Eye Proteins / Q000032:analysis / Q000235:genetics*; D007737:Kynurenine / Q000378:metabolism*; D009154:Mutation; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000032:analysis / Q000235:genetics*
D000199:Actins; D029721:Drosophila Proteins; D005136:Eye Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D007737:Kynurenine; D014364:Tryptophan; D014366:Tryptophan Oxygenase; C121974:v protein, Drosophila