Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCβII correlates with intensified fear-induced conflict behavior

Klara R. Birikh, Ella H. Sklan, Shai Shoham, Hermona Soreq

Research output: Contribution to journalArticlepeer-review

Abstract

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 CβII (PKCβII), which is known to be involved in fear conditioning. In stress-responsive brain regions of normal FVB/N mice, the mild stress of i.p. injection increased AChE and PKCβII 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 FVB/N 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 PKCβII in stress-responsive brain regions. These findings are consistent with the hypothesis that stress-associated changes in cholinergic gene expression regulate neuronal PKCβII functioning, promoting.

Original languageEnglish
Pages (from-to)283-288
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number1
DOIs
StatePublished - 7 Jan 2003
Externally publishedYes

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