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Markus Babst

assistant Professor of Biology

Diploma Federal Institute of Technology, Switzerland

Ph.D. Federal Institute of Technology, Switzerland

Research

References

babst@biology.utah.edu

 

Research

Eukaryotic cells continuously remove transmembrane proteins from the plasma membrane by endocytosis and deliver them to the lumen of lysosomes for degradation (see Figure). This protein degradation pathway plays an essential role not only in maintaining cellular homeostasis but also act to quickly and dramatically change the protein composition of the surface during processes such as cell differentiation.

The topological problem of degrading plasma membrane proteins in the lumen of the lysosome is solved in the formation of endosomal structures called 'multivesicular bodies' (MVBs) (see Figure). MVBs are part of the endosomal system of eukaryotic cells and are formed by invagination and budding of vesicles from the limiting membrane of endosomes into the lumen of the compartment. During this process only endosomal transmembrane proteins destined for degradation are sorted into the forming vesicles and eventually delivered to the lysosome. The sorting process at the MVB has been shown to be regulated by ubiquitination of the cargo protein.

The goal of my lab is to understand the molecular mechanisms involved in the formation of MVBs and the sorting of transmembrane proteins into the MVB vesicles. Up to date 18 highly conserved proteins have been identified that are required in both yeast and mammalian cells for MVB formation. The majority of these 18 proteins are part of three large protein complexes called ESCRT-I, ESCRT-II and ESCRT-III (Endosomal Sorting Complex Required for Transport). The ESCRT complexes act together on endosomes to regulate both the sorting of transmembrane proteins destined for degradation as well as the formation of MVB vesicles.

My lab uses a combination of yeast genetics, cell biology and biochemistry to gain insight into the function of the ESCRT proteins. We utilize the powerful genetic system of yeast to obtain interesting new mutants that are deficient in certain aspects of the MVB pathway. The function and interactions of the proteins encoded by these genes are then characterized by cell biological methods and biochemistry in both yeast and mammalian cells. Our eventual goal is to identify and purify the proteins required for MVB formation and biochemically reconstitute their function in vitro.

Cell surface proteins are endocytosed and transported to an endosomal structure called 'Multivesicular Body' (MVB). At the MVB monoubiquitinated transmembrane proteins are sorted into the forming vesicles. The MVB vesicles are delivered to the lumen of the lysosome for degradation.

References