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Movement Retraining using Real-time Feedback of Performance
Published on: January 17, 2013
ERLIN2-Ca2+-CREB signaling coordinates circadian timing via CRY1/CRY2 feedback
Yuwen Chen1, Jiaxin Lin1,2, Zongyou Zou1
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
None:
Circadian regulation in peripheral cells depends on calcium dynamics, but the upstream mechanisms remain unclear. We identify endoplasmic reticulum lipid raft-associated protein 2 (ERLIN2) as a regulator of the peripheral clock. Knockdown and overexpression of ERLIN2 in C2C12 skeletal muscle cells show that ERLIN2 positively regulates cryptochrome circadian regulator 1/2 (CRY1/2) transcription and maintains rhythmicity. ERLIN2 regulates inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release and activates the calcium/calmodulin-dependent protein kinase II (CaMKII)-mitogen-activated protein kinase (MAPK)-cAMP response element-binding protein (CREB) pathway. ATP induced IP3R-dependent Ca2+ transients, CREB phosphorylation, and Per1 expression, reshaping circadian rhythm, effects blocked by IP3R, Ca2+, or CaMKII inhibition. CRY1 enhances and CRY2 suppresses CREB signaling, establishing a feedback loop with ERLIN2. This ERLIN2-Ca2+-CREB-CRY1/2 axis couples membrane contact sites to circadian regulation. Impact statement This study reveals ERLIN2 as a key regulator linking calcium signaling to circadian rhythms, establishing an ERLIN2-Ca2+-CREB-CRY1/2 axis that advances understanding of cellular clock control.
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