Sequential protein glycosyla tion in the ER is important in maintaining the quality control of glycoproteins through folding and ER asso ciated protein degradation. Moreover, its defects could also interfere with the intracellular trafficking and secre tion of glycoproteins. Therefore, suitable regulation of aintain ER homeostasis. As the CRELD proteins have www.selleckchem.com/products/arq-197.html multiple EGF like domains, they are considered to be cell adhesion molecules. It has been reported that missense mutations in the CRELD1 gene increases an individuals susceptibility to atrioventricular septal defects, but the physiological roles of these family members remain poorly understood. In contrast to CRELD1, CRELD2 lacks a transmembrane domain in the C terminal region. Ortiz et al.

reported that the overexpression of CRELD2 impairs the membrane transport of acetylcholine receptor a4 b2 in Xenopus lae vis oocytes. We recently demonstrated that the CRELD2 gene is one of the downstream targets of ATF6 and that its product is predominantly localized in the ER Golgi apparatus. Interestingly, the mouse model for multiple epiphyseal dysplasia, which specifically expresses a mutation in matrilin 3, was reported to induce CRELD2 mRNA expression and other ER stress inducible genes as the symptoms progressed. According to these reports, CRELD2 seems to be involved in the folding, processing and transport of some proteins under pathophysiological conditions, though the precise role of CRELD2 remains to be determined.

Furthermore, we believe that the sharing of the ERSE motif in the CRELD2 ALG12 gene pair may be advantageous in regulating ER homeostasis under var ious ER stress conditions, even though it is unlikely that the CRELD2 and ALG12 proteins function by directly interacting with each other. Conclusion In this study, we first demonstrate that both the CRELD2 and ALG12 genes, which form a bidirectional gene pair, are potent ER stress inducible genes. Our pre sent results indicate that the CRELD2 ALG12 gene pair could be asymmetrically regulated by multiple transcrip tional factors in addition to ATF6. Because the CRELD2 ALG12 gene pair contains an evolutionally conserved ERSE motif, the cooperative induction of these genes may play important roles in confronting ER stresses and in appropriately regulating ER homeostasis and cell fates, together with other ER stress inducible Batimastat genes. Therefore, further characterization of the CRELD2 ALG12 gene pair may provide new insights into the complex transcriptional regulation of ER stress inducible genes as well as into the onset and progression of various ER stress associated diseases. Methods Cell culture and treatment Neuro2a cells were maintained in Dulbeccos Modified Eagles minimum essential Medium containing 8% fetal bovine serum.