Protein Trafficking (Ralf Schülein)
Introduction
Membrane proteins must have a correct subcellular location to exert their normal function. To allow correct protein sorting, cells possess a complex transport system, the secretory pathway (Fig.1) Transport starts with the insertion of the proteins into the membrane of the endoplasmic reticulum (ER), a process mediated by the protein-conducting translocon complex. Folding of the proteins is checked by a quality control system (QCS) and only correctly folded forms are allowed to enter the vesicular transport via the ER/Golgi intermediate compartment (ERGIC) and the individual compartments of the Golgi apparatus to the plasma membrane. Mutations in the genes of membrane proteins frequently lead to misfolded proteins failing to pass the QCS. These proteins are retained intracellularly, finally degraded and may cause consequently inherited disorders. To this group of diseases belong e.g. mucoviscidosis (mutations in the cystic fibrosis transmembrane conductance regulator protein, CFTR) and X-linked nephrogenic diabetes insipidus (NDI; mutations in the vasopressin V2 receptor, V2R). The Protein Trafficking group is interested in the quality control mechanisms of mutant GPCRs in order to identify new drugs influencing folding and transport processes. Moreover, we study the influence of the ER insertion mechanisms on establishing defined receptor densities at the cell surface and develop new methods for the subcellular localization of GPCRs
