| First Author | Szabo E | Year | 2008 |
| Journal | J Cell Biol | Volume | 182 |
| Issue | 1 | Pages | 103-16 |
| PubMed ID | 18606846 | Mgi Jnum | J:138195 |
| Mgi Id | MGI:3804552 | Doi | 10.1083/jcb.200712078 |
| Citation | Szabo E, et al. (2008) Calreticulin inhibits commitment to adipocyte differentiation. J Cell Biol 182(1):103-16 |
| abstractText | Calreticulin, an endoplasmic reticulum (ER) resident protein, affects many critical cellular functions, including protein folding and calcium homeostasis. Using embryonic stem cells and 3T3-L1 preadipocytes, we show that calreticulin modulates adipogenesis. We find that calreticulin-deficient cells show increased potency for adipogenesis when compared with wild-type or calreticulin-overexpressing cells. In the highly adipogenic crt(-/-) cells, the ER lumenal calcium concentration was reduced. Increasing the ER lumenal calcium concentration led to a decrease in adipogenesis. In calreticulin-deficient cells, the calmodulin-Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) pathway was up-regulated, and inhibition of CaMKII reduced adipogenesis. Calreticulin inhibits adipogenesis via a negative feedback mechanism whereby the expression of calreticulin is initially up-regulated by peroxisome proliferator-activated receptor gamma (PPAR gamma). This abundance of calreticulin subsequently negatively regulates the expression of PPAR gamma, lipoprotein lipase, CCAAT enhancer-binding protein alpha, and aP2. Thus, calreticulin appears to function as a Ca(2+)-dependent molecular switch that regulates commitment to adipocyte differentiation by preventing the expression and transcriptional activation of critical proadipogenic transcription factors. |
