Contact

Prof. Dr. Ralf Schülein

phone +49 30 94793 255

Fax +49-30-94793-109

schuelein(at)fmp-berlin.de

Protein Trafficking (Ralf Schülein)

Introduction

G protein-coupled receptors (GPCRs) are the most important drug targets. Like other integral membrane proteins, they must reach their correct subcellular compartment (usually the plasma membrane) to function correctly. Transport is enabled by the secretory pathway of the cells and starts with the signal sequence-mediated insertion of the GPCRs into the membrane of the endoplasmic reticulum (ER) via the protein-conducting translocon complex (Fig. 1). In the ER, GPCRs are folded and then transported in the membrane of vesicles through the individual compartments of the Golgi apparatus to the plasma membrane. The ER insertion of GPCRs and other membrane proteins is mediated by two types of signal sequences of the proteins. The majority possess signals forming part of the mature protein (“signal anchor sequence”; usually TM1). A smaller group, however, possesses additional N-terminal signal peptides that are cleaved off during the insertion process. We have studied in the last years why some GPCRs require these cleavable signal peptides whereas others do not. Our main model proteins have been the corticotropin-releasing factor receptors (CRF receptors), which play a major role in the development of anxiety and depressive disorders. We also try to develop novel biosynthesis inhibitors for specific GPCRs targeting their signal sequences and to develop inhibitors of the translocon complex in general. Recently, we also started to analyse the influence of cell aging processes on GPCR trafficking and signalling.

 

 

Fig. 1. Transport of integral membran proteins along the secretory pathway. In the beginning, proteins are integrated into the ER membrane by the translocon complex (Tr). This process is facilitated by signal sequences of the proteins. Two types of signal sequences are known: signal peptides (SP), which are cleaved-off following ER insertion, or signal anchor sequences (SAS) which form part of the mature proteins. In the ER, proteins are folded and transported in the membrane of vesicles via the individual compartments of the Golgi apparatus to the plasma membrane.

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)
info(at)fmp-berlin.de