MECHANISMS COUPLING PROTEIN FOLDING AND TRANSPORT AT THE ER-GOLGI INTERFACE: ROLE IN F5F8D AND OTHER DISEASES

Our bodies are composed by zillions of cells, which must work in the most strictly coordinated way. To do so, our cells continuously exchange information, by releasing messages under the form of secretory proteins (hormones, cytokines, antibodies). These messages are selectively deciphered by specific receptors (special proteins mounted on the external surface of our cells), very much like a key opens a given door. This implies that both keys and locks be perfectly shaped. Opening the wrong door (or not opening one when necessary) can cause disease. It is nor surprising, therefore, that our cells spend a tremendous amount of energy in producing perfect proteins. They are very attentive in blocking the release of bad ones, which are recognized and destroyed, the building blocks being recycled. At the same time, cells care about efficiency: good proteins must be secreted abundantly and rapidly. Think about the need of producing many good antibodies when you are ill. We are beginning to understand the molecular machines that cells evolved to cope with these problems. This knowledge is rapidly translating into the understanding of the causes of some genetic disorders, and will ultimately allow designing the best therapies. Our work focuses on a general mechanism that our cells utilize to inspect, select and transport secretory proteins. One rare bleeding disorder is caused by defects in this protein machine. As other diseases are likely caused by similar problems, we need to dissect the mechanisms that couple efficiency and fidelity in the protein factory of our cells. Only by knowing all the key components, we will be able to fix the molecular machines and cure the diseases.