Daily oscillation of phospholipase C beta4 in the mouse suprachiasmatic nucleus.
An endogenous biological clock located in the hypothalamic suprachiasmatic nucleus (SCN) regulates the timing of an organism's physiology and behavior. A variety of receptors are found on SCN pacemaker cells which permit the clock mechanism to respond to extra- and intra-SCN chemical messengers. A subset of these receptors is coupled to G-proteins, which when bound, lead to the activation of a variety of intracellular signaling cascades. One common signaling pathway employs the phosphotidylinositol-specific phospholipase C enzyme to increase intracellular calcium levels. A specific isoform of this enzyme, phospholipase C beta4, is of particular interest to circadian biologists because in its absence, mice display a circadian phenotype. Moreover, it has been shown to be associated with receptor types that are involved in clock resetting. Despite compelling data that this enzyme could be a critical component of an intracellular signaling pathway in the SCN, no study to date has investigated the possible oscillation of phospholipase C in any mammalian tissue. In the present study, we analyzed the temporal variation in the number of phospholipase C beta4 immunoreactive cells in the SCN. Herein, we show that PLCbeta4 levels oscillate in the SCN of mice housed in a light:dark photoperiod. Protein levels reached a significant peak during the early night and a trough during the day. The oscillation was considerably damped in the SCN of mice housed in constant dark conditions indicating the cycle is photoperiod-dependent. These data are critical to understanding the temporal regulation of a variety of inputs to the mammalian central circadian clock.
Jenkins
Travis C
TC
Department of Biology, College of Charleston, 66 George Street, Charleston, SC 29424, USA.
Andrews
J Blakely
JB
Meyer-Bernstein
Elizabeth L
EL
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D002940:Circadian Rhythm / Q000502:physiology*; D003624:Darkness; D003627:Data Interpretation, Statistical; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics; D056950:Period Circadian Proteins; D054799:Phospholipase C beta / Q000096:biosynthesis / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000201:enzymology*
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D054799:Phospholipase C beta