| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Research Abstract |
In cells, most of the secretory and membrane proteins are synthesized in the endoplasmic reticulum (ER), and only correctly folded proteins are transported to the Golgi apparatus for further processing. There are chaperone proteins such as GRP78, GRP94, calnexin, and calreticulin in the ER, and they assist the folding of newly synthesized or misfolded proteins. Still, it is expected that important chaperone proteins remains to be recovered in the ER.
In this study, I searched for new chaperone proteins in the ER, and analyzed its function to clarify the mechanisms of protein folding and the quality control in the ER.To clone new chaperone proteins, I employed supression subtractive hybridization (SSH) method from cells treated with ER stress, because chapereone proteins are expected to be upregulated by ER stress. I focused on an EST clone which was similar to α-mannosidase. After cloning the whole gene of this EST clone, I analyzed the fundction of this gene product in the cells, and named it as EDEM (ER degradation enhancing α-mannosidase-like protein). EDEM accelerated the degradation of misfolded glycoprotein in the ER, depending on the extent of mannose trimming of N-linked oligosaccharides, and expected to be the key molecule of the ER associated degradation or ER quality control.
|
