| First Author | Cal-Kayitmazbatir S | Year | 2021 |
| Journal | FEBS J | Volume | 288 |
| Issue | 2 | Pages | 614-639 |
| PubMed ID | 32383312 | Mgi Jnum | J:317207 |
| Mgi Id | MGI:6849439 | Doi | 10.1111/febs.15360 |
| Citation | Cal-Kayitmazbatir S, et al. (2021) CRY1-CBS binding regulates circadian clock function and metabolism. FEBS J 288(2):614-639 |
| abstractText | Circadian disruption influences metabolic health. Metabolism modulates circadian function. However, the mechanisms coupling circadian rhythms and metabolism remain poorly understood. Here, we report that cystathionine beta-synthase (CBS), a central enzyme in one-carbon metabolism, functionally interacts with the core circadian protein cryptochrome 1 (CRY1). In cells, CBS augments CRY1-mediated repression of the CLOCK/BMAL1 complex and shortens circadian period. Notably, we find that mutant CBS-I278T protein, the most common cause of homocystinuria, does not bind CRY1 or regulate its repressor activity. Transgenic Cbs(Zn/Zn) mice, while maintaining circadian locomotor activity period, exhibit reduced circadian power and increased expression of E-BOX outputs. CBS function is reciprocally influenced by CRY1 binding. CRY1 modulates enzymatic activity of the CBS. Liver extracts from Cry1(-/-) mice show reduced CBS activity that normalizes after the addition of exogenous wild-type (WT) CRY1. Metabolomic analysis of WT, Cbs(Zn/Zn) , Cry1(-/-) , and Cry2(-/-) samples highlights the metabolic importance of endogenous CRY1. We observed temporal variation in one-carbon and transsulfuration pathways attributable to CRY1-induced CBS activation. CBS-CRY1 binding provides a post-translational switch to modulate cellular circadian physiology and metabolic control. |
