Format

Send to

Choose Destination
Mol Cell Biol. 2011 Mar;31(6):1145-59. doi: 10.1128/MCB.00967-10. Epub 2011 Jan 10.

Derlin-2-deficient mice reveal an essential role for protein dislocation in chondrocytes.

Author information

1
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Rm. 361, Cambridge, MA 02142, USA.

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.

PMID:
21220515
PMCID:
PMC3067910
DOI:
10.1128/MCB.00967-10
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center