CHAPTER 1 PART 3

Current Research (Abstracts)

Proteins destined for locations along the secretory pathway are synthesized initially on the membrane bound ER. They are then transported to the ER lumen where they are unfolded and begin assembly. The protein folding is made possible by a type of protein known as molecular chaperones. These chaperones bind transiently to nascent polypeptide chains. These chaperones are thought to function through prohibiting an aggregation of these polypetide chains and maintaining them in appropriate conformations for folding and assembly. The nascent proteins which cannot unfold correctly or assemble correctly are retained within the ER and degraded as part of the systems "quality control". The primary purpose of this research is to shed light on the molecular chaperones of the ER and the mechanisms of quality control. Most recent research evolves around the discovery of such a chaperone known as calnexin. Its functions were studied by observing its interaction with a protein model that passes through the ER enroute to the cell surface.This model protein, known as the class I histocompatibility molecule, has an important immunilogical function in it that binds peptide fragments of viral proteins while in the ER, and carries them away to the cells surface, where they can be recognizwd by the cell's immune system and destroyed.Several in vivo systems have allowed interference with the calnexin action thereby showing that calnexin facilitates the folding and assembly of class I molecules. It has also been demonstrated that the calnexin retains those class I mutants which can not fold or assemble properly, thereby functioning as a part of the quality control unit. Recently it was found that calnexin recognizes nacent proteins in an unusual way.Calnexin contains lectin properties that allow it to bind to oligosaccharide chains attached to proteins as they enter the ER. After this binding, calnexin associates with the polypeptide portion of the nacent protein to facilitate the unfolding and assembly process. Protein Folding and Quality Control Within the Endoplasmic Reticulum by David B. Williams (1998) One of the chief functions of the golgi apparatus is glycosylation.The current evidence shows that the golgi apparatus is sub-compartmentalized. Withinb these compartments, enzymes which are involved in processing glycocomjugates, are stored in the sequence in which they act.The purpose of this investigation is to further define the compartmentalization of the golgi apparatus by studying the glycolyzation in a number of different cell types. The methodology used here of high resolution post-embedding immunocytochemistry where highly purified and well characterized monclonal and polyclonal antibodies were employed.Current investigations of the golgi apparatus shows a distribution of a terminally-acting galactosyltransferase that adds galactoes residues in a 1,3 linkage to penultimate galactose. At the same time there are antibodies that also rcognize the galactosyltransferase which adds the penultimate galactose to the oligosaccharide chain.In comparing the two it is hoped that a determination can be made as to the extent of the golgi apparatus subcompartmentalization with respect to glycosylation. Serial thin sections were made throgh the entire cisternal stack in order to determine the distribution of glycosyltransferase within the entire golgi apparatus. A current model of the golgi apparatus sugests that these proteins must be sequestered away from the rim of the cisternae. This is due to the observation that the rims tend tp pinch off from one cisternae and carry secretory material to the next cisternae where it fuses to it. In addition to the modification of oligosaccharide chains as they cross the golgi apparatus, some glycosyltransferases have even been found at the cell surface. In such a case galactosyltranferase has played an important role in the cell migration on the extracellular matrix and in the inhibition of fertilization. Glycosylation Research by D.J. Taatjes © BOTRESEARCH USA 1998-2008