Research group Martin Spiess
Membrane proteins and their transport in the cell
How are membrane proteins correctly assembled in the cell membrane and transported through the complex network of organelles in the cell? Errors in protein transport may result in disease.
All of our cells are surrounded by a lipid membrane, just as all the organelles within the cell are separated from each other by membranes. These membranes consist of lipids and membrane proteins that are first assembled in the membrane of the endoplasmic reticulum (ER), a network spanning the entire cell. Membrane proteins are then sorted and transported to their intended organelles.
Folding of membrane proteins
Just how proteins fold into the lipid membrane is determined by their amino acid sequence. Our goal is to understand the process of protein folding and orientation in cell cultures, and in yeast cells as a model organism.
Protein transport between organelles typically involves formation of a vesicle containing the protein to be transported from the membrane. The vesicle then fuses with the target organelle. Our research focuses on this mechanism and its regulation; in particular, we are looking at the uptake of proteins at the cell surface and their recycling.
Although the hormone vasopressin itself is not a membrane protein, it is also transported from the ER to the cell surface. Mutations that disrupt its export cause the cells to die and result in diabetes insipidus, a rare metabolic disorder. We have discovered that these mutations give rise to protein aggregates, similar to those seen in neurological conditions such as Alzheimer's disease, and we are investigating how this happens.