| Description |
Transporters must be sustained in proper working function at the plasma membrane to prevent serious harm to a cell. A dysfunctional transporter may cause leaking of ions, loss of membrane potential, disturbed cell signaling, and even cell death. Therefore, cautious monitoring of transporters occurs at the plasma membrane. A transporter which becomes unfolded or unstable is quickly endocytosed and taken to the early endosome compartment of the cell. However, these unfolded transporters are not automatically degraded, as a cell attempts to preserve them by allowing time for refolding. It is this process we refer to as quality control: where the decision is made whether to degrade the dysfunctional protein to maintain cell integrity or attempt to refold it to conserve energy. The endosome provides a safe place where this decision can be made. Properly folded and functional transporters will return to the plasma membrane to resume pumping, while those deemed dysfunctional will continue on to be degraded. In the case of the yeast uracil transporter Fur4, unfolded/destabilized Fur4 is ubiquitinated (signal for degradation added) by Rsp5, the only ubiquitin ligase known to work at the plasma membrane in yeast. After being endocytosed and brought to the early endosome, the decision to degrade or recycle Fur4 is made there. How exactly that quality control decision is made is not well understood. It is known that ubiquitination status plays a major role in that decision, and that both ubiquitination and deubiquitination can occur at the early endosome. However, studies have shown that Fur4 can recycle in spite of being in a ubiquitin tagged state in some mutant strains, suggesting the quality control decision is not so black and white. We attempt to elucidate this quality control process. Our results, and those published, have led us to a model whereby ubiquitination status is not the sole deciding factor involved in sorting at the early endosome, but where retention of ubiquitinated cargo is actually the key sorting step. Herein we describe a complex of proteins working together at the early endosome to carry out quality control. |
