The unfolded protein response

Published on February 2, 2012   30 min

Other Talks in the Series: Protein Homeostasis

Hello. This is Kazutoshi Mori from Kyoto University. The title of my talk is the unfolded protein response.
Protein is a polypeptide when synthesized according to the central dogma, and it needs to gain correct tertiary and quaternary structure to fulfill its function as assigned by genetic code. For example, growth hormone receptor must have this beautiful structure to bind to growth hormone. However, correct folding of proteins is quite difficult inside the cell, which contains proteins at very high concentrations. So protein folding is considered to be the last hurdle for the expression of genome information.
Secretory proteins, such as growth hormone, and transmembrane proteins, such as growth hormone receptor, are folded and assembled in the endoplasmic reticulum, ER, the first organelle they encounter after synthesis on the membrane-bound ribosome. The ER contains a number of molecular chaperones and folding enzymes abundantly that assist productive folding of these proteins, and only correctly folded molecules are allowed to move along the secretory pathway, and reach their final destinations. Because the cell synthesizes a large number of proteins, some of them, said to be less than 10%, are still unfolded or misfolded, even after the assistance from chaperones. They are retrotransported back to the cytosol to be degraded by the ubiquitin proteasome system. This process is called the ER-associated degradation, ERAD. Thus, quality control system operates in the ER.