Phospholipase C isozymes selectively couple to specific neurotransmitter receptors.
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, beta1-beta4, but their functions in vivo are not known. Here we investigate the role of PLC-beta1 and PLC-beta4 in the brain by generating null mutations in mice: we found that PLCbeta1-/- mice developed epilepsy and PLCbeta4-/- mice showed ataxia. We determined the molecular basis of these phenotypes and show that PLC-beta1 is involved in signal transduction in the cerebral cortex and hippocampus by coupling predominantly to the muscarinic acetylcholine receptor, whereas PLC-beta4 works through the metabotropic glutamate receptor in the cerebellum, illustrating how PLC-beta isoenzymes are used to generate different functions in the brain.
Kim
D
D
Department of Life Science, Pohang University of Science and Technology, Republic of Korea.
Jun
K S
KS
Lee
S B
SB
Kang
N G
NG
Min
D S
DS
Kim
Y H
YH
Ryu
S H
SH
Suh
P G
PG
Shin
H S
HS
D000818:Animals; D001259:Ataxia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002531:Cerebellum / Q000002:abnormalities; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004827:Epilepsy / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology; D016296:Mutagenesis; D010716:Phosphatidylinositols / Q000378:metabolism; D054799:Phospholipase C beta; D010879:Piperazines / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D018721:Muscarinic Agonists; D010716:Phosphatidylinositols; D010879:Piperazines; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D017366:Serotonin Receptor Agonists; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D002217:Carbachol; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse; C518043:Plcb4 protein, mouse; C015068:1-(3-chlorophenyl)piperazine