| Abstract: | ["Transport into the endoplasmic reticulum (ER) is the first biosynthetic step for secretory proteins. This highly regulated process is critical for the biosynthesis of many membrane proteins as well, and requires cytosolic and ER proteins, many of which were first identified using yeast genetics. The Zimmermann group studies the protein translocase that mediates the cotranslational insertion of proteins into the membrane of the pancreatic endoplasmic reticulum. Biochemical, biophysical, structural, and cell biological approaches are combined in order to elucidate the mechanism and the regulation of components of this protein translocase. The products of SIL1, SEC62, and SEC63 genes act in concert with the Sec61 complex and the molecular chaperones BiP and Grp170 to transport proteins into the ER. A special emphasis is placed on transport components of the ER-membrane that associate with the tunnel exit of cytosolic ribosomes (such as Sec61 complex, ERj1, Sec62). Interestingly, recent genetic work has linked mutations in the human and murine SIL1 genes to neurodegeneration and mutations in the human SEC63 gene to autosomal dominant polycystic liver disease. Furthermore, mutations in the SEC63 gene and overexpresion of the SEC62 gene are associated with variious human cancers."] |
