Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCbeta II correlates with intensified fear-induced conflict behavior.
Behavioral reactions to stress are altered in numerous psychiatric and neurodegenerative syndromes, but the corresponding molecular processes and signal transduction pathways are yet unknown. Here, we report that, in mice, the stress-induced splice variant of acetylcholinesterase, AChE-R, interacts intraneuronally with the scaffold protein RACK1 and through it, with its target, protein kinase CbetaII (PKCbetaII), which is known to be involved in fear conditioning. In stress-responsive brain regions of normal FVBN mice, the mild stress of i.p. injection increased AChE and PKCbetaII levels in a manner suppressible by antisense prevention of AChE-R accumulation. Injection stress also prolonged conflict between escape and hiding in the emergence into an open field test. Moreover, transgenic FVBN mice overexpressing AChE-R displayed prolonged delay to emerge into another field (fear-induced behavioral inhibition), associated with chronically intensified neuronal colabeling of RACK1 and PKCbetaII in stress-responsive brain regions. These findings are consistent with the hypothesis that stress-associated changes in cholinergic gene expression regulate neuronal PKCbetaII functioning, promoting fear-induced conflict behavior after stress.
Birikh
Klara R
KR
Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Israel.
Sklan
Ella H
EH
Shoham
Shai
S
Soreq
Hermona
H
D000110:Acetylcholinesterase / Q000235:genetics* / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003220:Conflict, Psychological; D005239:Fear / Q000502:physiology*; D014644:Genetic Variation; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000201:enzymology / Q000502:physiology; D016716:PC12 Cells; D010455:Peptides / Q000378:metabolism*; D010673:Pheochromocytoma; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051381:Rats; D011930:Reaction Time; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013315:Stress, Psychological / Q000503:physiopathology; D014162:Transfection
D007527:Isoenzymes; D010455:Peptides; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C070301:peptide I; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D000110:Acetylcholinesterase