Abstract

Approximately 25% of all genes encode integral membrane proteins that must be selectively targeted to and inserted into various intracellular membranes. These hydrophobic membrane proteins must necessarily transit the cytosol en route to their final destination. Our group has been investigating how cytosolic factors shield these membrane proteins to prevent aggregation and how they are correctly targeted to their final destination. These destinations include the endoplasmic reticulum, mitochondria, or the proteasome. Over the past several years, we have begun to identify and analyze the factors involved in membrane protein traffic and degradation in the cytosol. These include the factors for tail-anchored membrane protein targeting to the ER and degradation factors for elimination of mis-targeted membrane proteins. We are now dissecting the inter-relationships between these various factors to determine how membrane proteins are triaged appropriately to maintain cytosolic protein homeostasis.