Contribution of calumin to embryogenesis through participation in the endoplasmic reticulum-associated degradation activity
| Autor: | Nobuyuki Takakura, Takeshi Yamashita, Shinichiro Yamamoto, Masaya Matsubayashi, Sho Kakizawa, Shinji Komazaki, Hiroyasu Kidoya, Masako Osaki, Tetsuo Yamazaki, Daiju Yamazaki |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Calumin
Cholera Toxin Protein Folding medicine.medical_specialty Embryonic Development Apoptosis Mice Transgenic Context (language use) macromolecular substances Endoplasmic-reticulum-associated protein degradation Biology Endoplasmic Reticulum Cell Line Mice Internal medicine CCDC47 medicine Animals Humans RNA Small Interfering Yolk sac Molecular Biology Yolk Sac Endoplasmic reticulum Endoderm HEK 293 cells Embryogenesis Membrane Proteins Endoplasmic Reticulum-Associated Degradation Cell Biology ERAD Endoplasmic Reticulum Stress Cell biology Secretory cells Mice Inbred C57BL HEK293 Cells medicine.anatomical_structure Endocrinology alpha 1-Antitrypsin Mutation embryonic structures Unfolded protein response RNA Interference ER stress Developmental Biology |
| Zdroj: | Developmental Biology. 393(1):33-43 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2014.06.024 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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