Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and the ubiquitin ligase Rsp5

摘要

The plasma membrane that surrounds cells contains many different proteins that perform tasks such as detecting signals sent to the cell, and transporting molecules into or out of the cell. To adapt to changing conditions, cells remodel their membrane to change how much of each type of protein is present. A process called endocytosis—where part of the plasma membrane and the proteins it contains buds off into the cell—plays an important role in this remodeling. The fate of a membrane protein after endocytosis can depend on whether a protein ‘tag’ called ubiquitin has been added to it. Ubiquitin-marked proteins bud off into the cell and are then sent to cell structures called lysosomes to be degraded, whereas unmarked proteins are recycled back to the plasma membrane. Yeast cell membranes contain a protein called Jen1 that transports certain molecules, including one called lactate that can be used as fuel for growth. However, glucose is a preferred nutrient for yeast, so when glucose is available, another protein called Rod1 becomes activated and promotes the addition of ubiquitin to Jen1, and hence its degradation. This means that the cells can no longer use lactate as a source of energy. However, it was not known where in the cell the Rod1 protein does this. Becuwe and Léon labeled proteins involved in endocytosis with fluorescent tags and used microscopy to observe their fate in live yeast cells exposed to glucose. This revealed two roles for Rod1. At the plasma membrane, Rod1 helps Jen1 to be taken into the cell in the early stages of endocytosis. But unexpectedly, Rod1 is also found at a cellular structure called the trans-Golgi network, small membrane sacs that are typically responsible for packaging proteins so they can be transported to a new destination, in particular the plasma membrane. This suggests that Rod1 can also act at this location in the cell. When the proteins responsible for maintaining transport to the trans-Golgi network are inhibited, Jen1 is no longer degraded, even when glucose is present; instead, Jen1 is recycled back to the plasma membrane. Becuwe and Léon therefore propose that a second level of control of the degradation of plasma membrane proteins occurs in the trans-Golgi network, and so this compartment has an essential role in sorting proteins for degradation or recycling. The group of proteins that Rod1 belongs to, named arrestins, has been suggested to play important roles in several diseases, including diabetes and cancer. As many of the features of the endocytic pathway are conserved in a broad range of species, arrestins may also be important for controlling the fate of membrane proteins at multiple places in mammalian cells. However, further work is required to confirm this.