Derlin-2-Deficient Mice Reveal an Essential Role for Protein Dislocation in Chondrocytes
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Author(s)
Ploegh, Hidde
Kim, Jun
Dougan, Stephanie K.
Hu, Chih-Chi Andrew
Paquet, Marie-Eve
Greenblatt, Matthew B.
Lilley, Brendan N.
Watson, Nicki
Date Issued
January 2011
Journal
Molecular and Cellular Biology
Publisher
American Society for Microbiology
Citation
Dougan, S. K. et al. “Derlin-2-Deficient Mice Reveal an Essential Role for Protein Dislocation in Chondrocytes.” Molecular and Cellular Biology 31.6 (2011): 1145–1159.
Version
Author's final manuscript
Abstract
Protein quality control is a balance between chaperone-assisted folding and removal of misfolded proteins from the endoplasmic reticulum (ER). Cell-based assays have been used to identify key players of the dislocation machinery, including members of the Derlin family. We generated conditional knockout mice to examine the in vivo role of Derlin-2, a component that nucleates cellular dislocation machinery. In most Derlin-2-deficient tissues, we found constitutive upregulation of ER chaperones and IRE-1-mediated induction of the unfolded protein response. The IRE-1/XBP-1 pathway is required for development of highly secretory cells, particularly plasma cells and hepatocytes. However, B lymphocyte development and antibody secretion were normal in the absence of Derlin-2. Likewise, hepatocyte function was unaffected by liver-specific deletion of Derlin-2. Whole-body deletion of Derlin-2 results in perinatal death. The few mice that survived to adulthood all developed skeletal dysplasia, likely caused by defects in collagen matrix protein secretion by costal chondrocytes.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1128/mcb.00967-10
