Phospholipase C isozymes selectively couple to specific neurotransmitter receptors

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A variety of extracellular signals are transduced across the cell membrane by the enzyme phosphoinositide-specific phospholipase C-beta (PLC-beta) coupled with guanine-nucleotide-binding G proteins'. There are four isoenzymes of PLC-beta, beta 1-beta 4, but their functions in vivo are not known. Here we investigate the role of PLC-beta 1 and PLC-beta 4 in the brain by generating-null mutations in mice: we found that PLC beta 1(-/-) mice developed epilepsy and PLC beta 4(-/-) mice showed ataxia. We determined the molecular basis of these phenotypes and show that PLC-beta 1 is involved in signal transduction in the cerebral cortex and hippocampus by coupling pre-dominantly to the muscarinic acetylcholine receptor, whereas PLC-beta 4 works through the metabotropic glutamate receptor in the cerebellum, illustrating how PLC-beta isoenzymes are used to generate different functions in the brain.
Publisher
MACMILLAN MAGAZINES LTD
Issue Date
1997-09
Language
English
Article Type
Article
Keywords

PHOSPHOINOSITIDE HYDROLYSIS; SIGNAL-TRANSDUCTION; ALZHEIMERS-DISEASE; MESSENGER-RNAS; RAT-BRAIN; EPILEPSY; SEIZURES; MICE; LOCALIZATION; INTERNEURONS

Citation

NATURE, v.389, no.6648, pp.290 - 293

ISSN
0028-0836
URI
http://hdl.handle.net/10203/23310
Appears in Collection
BS-Journal Papers(저널논문)
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