2001 Fiscal Year Final Research Report Summary
Studies on dynamics of nascent proteins upon folding
| Project/Area Number |
12480183
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Sapporo Medical University School of Medicine |
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Principal Investigator |
WADA Ikuo Sapporo Medical University, Medicine, Associate Professor, 医学部, 助教授 (40182969)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Endoplasmic reticulum / Folding / COP II / Quality control / Membrane dynamics |
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| Research Abstract |
1. Some misfolded proteins in the secretory pathway are degraded at the level of the endoplasmic reticulum (ER) by proteasome. We reported that a novel protein, EDEM, accelerates the proteasoome-mediated degradation. Because EDEM is likely an inactive form of ER mannosidasel, we suggested that EDEM may be a receptor for misfolded proteins bearing Man8 oligosaccharides.
2. Folded secretory proteins are exported from the transitional elements of the ER (tER). We reported that the process is inhibited by diacylglycerol kinase delta (DGKd) whose functon had not been assigned. The action appeared to be mediated by attachment of COPII coat to tER. Targetting of DGKd requires C-terminus SAM domain, and, suprisingly, does not require the enzyme activity but depends on N-termmus PH domain.
3.Oculocytanous albinism type I (OCA I) is caused by mutations of tyrosinase. We reported that tyrosinase OCAI mutants are retained-in the ER until dissociation from calnexin and immediately degraded by proteasome. Furthermore, we reported that wild type tyrosinase is retained in the ER by mutations in tyrosinase-related protein-1, which seems to a molecular basis for OGA3.
4. We found that the degradtion accelarated by EDEM does not involve recycling through ERGIC but the one stimulated by ER mannosidase I requires recycling.
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