细胞质基质与与内膜系统.ppt

* * Schematic representation of the ubiquitin-proteasome pathway and the secretory pathway with the quality control machinery that dislocate misfolded proteins from the ER. The acronyms of the transcripts contained in IMP1 granules are indicated in red. For full names refer to Table I (1). Proteins to be glycosylated enter the ER in an unfolded state upon co-translational translocation through the heterotrimeric Sec61 channel. Nascent polypeptides are covalently modified by attachment of high mannose core oligosaccharides. N-Linked glycosylation is carried out by the oligosaccharyltransferase complex. Both DAD1 and DC2 have been identified as members of the large oligosaccharyltransferase complex (54). In the ER, the core glycan Glc3Man9GlcNAc2 is trimmed by ER glucosidases I and II and ER mannosidase I (MANBAL and MANEAL) before glycoproteins become competent to leave this compartment. Biosynthesis of a glycosylphosphatidylinositol anchor depends on the presence of phosphatidylinositol glycan (PIG) of which PIGF, -H, and -S are members (2). If proteins are correctly folded they can leave the ER through COPII-coated vesicles, which coordinate the budding of transport vesicles from the endoplasmic reticulum in the initial step of the secretory pathway. Among others the Sec13/31 subcomplex takes part in organizing this process (55). Another component necessary for this transport is Yif1 (56). In the Golgi apparatus, proteins can be packed into secretory vesicles at the trans-Golgi network where members of the secretory carrier membrane protein (SCAMP) gene family and Arf1 are located (57). Proteins destined for the lysosome are subjected to vacuolar protein sorting (VPS) (3). If the proteins are incorrectly folded, they are subjected to ER-associated degradation or unfolded protein response (4). This results in the cytosolic degradation by the ubiquitin-proteasome system after dislocation of the protein through the Sec61 pore (5). RING finger proteins (RNFs) have been