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Dev Biol. 2014 Sep 1;393(1):33-43. doi: 10.1016/j.ydbio.2014.06.024. Epub 2014 Jul 8.

Contribution of calumin to embryogenesis through participation in the endoplasmic reticulum-associated degradation activity.

Author information

1
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; Department of Molecular Cell Biology and Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8505, Japan. Electronic address: yamashin@tokushima-u.ac.jp.
2
Department of Molecular Cell Biology and Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8505, Japan.
3
Saitama Medical University, Saitama 350-0495, Japan.
4
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
5
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

Abstract

Calumin is an endoplasmic reticulum (ER)-transmembrane protein, and little is known about its physiological roles. Here we showed that calumin homozygous mutant embryos die at embryonic days (E) 10.5-11.5. At mid-gestation, calumin was expressed predominantly in the yolk sac. Apoptosis was enhanced in calumin homozygous mutant yolk sacs at E9.5, pointing to a possible link to the embryonic lethality. Calumin co-immunoprecipitated with ERAD components such as p97, BIP, derlin-1, derlin-2 and VIMP, suggesting its involvement in ERAD. Indeed, calumin knockdown in HEK 293 cells resulted in ERAD being less efficient, as demonstrated by attenuation in both degradations of a misfolded α1-antitrypsin variant and the ER-to-cytosol dislocation of cholera toxin A1 subunit. In calumin homozygous mutant yolk sac endoderm cells, ER stress-associated alterations were observed, including lipid droplet accumulation, fragmentation of the ER and dissociation of ribosomes from the ER. In this context, the ER-overload response, assumed to be cytoprotective, was also triggered in the mutant endoderm cells, but seemed to fully counteract the excessive ER stress generated due to defective ERAD. Taken together, our findings suggested that calumin serves to maintain the yolk sac integrity through participation in the ERAD activity, contributing to embryonic development.

KEYWORDS:

CCDC47; Calumin; ER stress; ERAD; Embryogenesis; Secretory cells

PMID:
25009997
DOI:
10.1016/j.ydbio.2014.06.024
[Indexed for MEDLINE]
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