FIGURE

Figure 8

ID

ZDB-FIG-230217-17

Publication

Fung et al., 2023 - Expression of the Z Variant of α1-Antitrypsin Suppresses Hepatic Cholesterol Biosynthesis in Transgenic Zebrafish

Other Figures

All Figure Page

Back to All Figure Page

Figure 8

Model for ERAD pathway interference between the ZAAT processing system and cholesterol biosynthesis. (A) In zebrafish expressing ZAAT, degradation of misfolded ZAAT via ERAD-L limits the ERAD machinery available for Insig turnover via ERAD-M. More Insig, therefore, remains bound to the Scap-Srebp2 complex in the ER membrane, reducing Srebp2 release from the ER and suppressing activation of the downstream cholesterol biosynthesis pathway. (B) Ablation of Erlec1 prevents the retrotranslocation of misfolded ZAAT via the Hrd1 ligase complex and redirects it to the gp78 complex, further reducing the capacity for Insig degradation and enhancing Srebp2 retention in the ER membrane. (C) The absence of Man1b1 proteins in zebrafish liver enhances ZAAT secretion, consistent with a role for Man1b1 in the Golgi in retrieving misfolded ZAAT that escaped the ERQC system and returning it to the ER.

Expression Data

Expression Detail

Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Int. J. Mol. Sci.