Muscarinic acetylcholine receptors induce the expression of the immediate early growth regulatory gene CYR61

被引:60
作者
Albrecht, C
von der Kammer, H
Mayhaus, M
Klaudiny, J
Schweizer, M
Nitsch, RM
机构
[1] Univ Zurich, Dept Psychiat Res, CH-8008 Zurich, Switzerland
[2] Slovak Acad Sci, Inst Chem, Bratislava 84238, Slovakia
[3] Univ Hamburg, Ctr Mol Neurobiol Hamburg, D-20246 Hamburg, Germany
关键词
D O I
10.1074/jbc.M003053200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In brain, muscarinic acetylcholine receptors (mAChRs) modulate neuronal functions including long term potentiation and synaptic plasticity in neuronal circuits that are involved in learning and memory formation. To identify mAChR-inducible genes, we used a differential display approach and found that mAChRs rapidly induced transcription of the immediate early gene CYR61 in HEK 293 cells with a maximum expression after 1 h of receptor stimulation. CYR61 is a member of the emerging CCN gene family that includes CYR61/CEF10, CTGF/FISP-12, and NOV; these encode secretory growth regulatory proteins with distinct functions in cell proliferation, migration, adhesion, and survival. We found that CYR61, CTGF, and NOV were expressed throughout the human central nervous system. Stimulation of mAChRs induced CYR61 expression in primary neurons and rat brain where CYR61 mRNA was detected in cortical layers V and VI and in thalamic nuclei. In contrast, CTGF and NOV expression was not altered by mAChRs neither in neuronal tissue culture nor rat brain. Receptor subtype analyses demonstrated that mi and m3 mAChR subtypes strongly induced CYR61 expression, whereas m2 and m4 mAChRs had only subtle effects. Increased CYR61 expression was coupled to mAChRs by both protein kinase C and elevations of intracellular Ca2+. Our results establish that CYR61 expression in mammalian brain is under the control of cholinergic neurotransmission; it may thus be involved in cholinergic regulation of synaptic plasticity.
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页码:28929 / 28936
页数:8
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