Lack of calbindin-D28k alters response of the murine circadian clock to light.
A strong stimulus adjusting the circadian clock to the prevailing light-dark cycle is light. However, the circadian clock is reset by light only at specific times of the day. The mechanisms mediating such gating of light input to the CNS are not well understood. There is evidence that Ca(2+) ions play an important role in intracellular signaling mechanisms, including signaling cascades stimulated by light. Therefore, Ca(2+) is hypothesized to play a role in the light-mediated resetting of the circadian clock. Calbindin-D28k (CB; gene symbol: Calb1) is a Ca(2+) binding protein implicated in Ca(2+) homeostasis and sensing. The absence of this protein influences Ca(2+) buffering capacity of a cell, alters spatio-temporal aspects of intracellular Ca(2+) signaling, and hence might alter transmission of light information to the circadian clock in neurons of the suprachiasmatic nuclei (SCN). We tested mice lacking a functional Calb1 gene (Calb1(-/-)) and found an increased phase-delay response to light applied at circadian time (CT) 14 in these animals. This is accompanied by elevated induction of Per2 gene expression in the SCN. Period length and circadian rhythmicity were comparable between Calb1(-/-) and wild-type animals. Our findings indicate an involvement of CB in the signaling pathway that modulates the behavioral and molecular response to light.
Stadler
Frédéric
F
Department of Medicine, Unit of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland.
Schmutz
Isabelle
I
Schwaller
Beat
B
Albrecht
Urs
U
D000818:Animals; D001483:Base Sequence; D064092:Calbindin 1; D064026:Calbindins; D020013:Calcium Signaling; D002540:Cerebral Cortex / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D056950:Period Circadian Proteins / Q000235:genetics; D010775:Photic Stimulation; D017440:Photoperiod; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D017931:DNA Primers; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D064030:S100 Calcium Binding Protein G