Cell surface trans-membrane (TM) proteins link the interior of the cell with the extra-cellular environment and
allow the cell to transport nutrients and to respond sensory information. To preserve the function of the plasma
membrane, quality control mechanisms recognize and eliminate defects in integral plasma membrane proteins.
Quality control mechanisms that function at the Endoplasmatic reticulum (ER) and the Golgi apparatus are well
understood. How cells recognize and specifically remove TM-proteins that suffer damage after insertion into the
plasma membrane is not known. Therefore I propose to study cellular mechanisms that underlie the quality control
of TM-plasma membrane proteins. Upon recognition of a defect, regulatory signals must link up with the
components of the endocytic machinery to selectively remove the damaged protein and transport it to the vacuole. I
will employ genetic screens in yeast to identify mechanisms for the recognition and selective turnover of damaged
plasma membrane proteins. The identification and characterization of components involved in plasma membrane
quality control might have fundamental significance in understanding the pathogenesis of conformational diseases
and in the maintenance of cellular homeostasis.