Search

Cholesterol is synthesized in the endoplasmic reticulum (RE) and then transported to cellular compartments whose functions require high cholesterol levels. Here, we describe the mechanism by which cholesterol is transported from the RE to the trans-Golgi network (TGN) by the protein OSBP (Oxysterol-Binding Protein). OSBP has two complementary activities. First, it tethers the RE to the TGN by forming a contact site where the two membranes are about twenty nanometers away. Then, it exchanges RE cholesterol for a TGN lipid, phosphatidylinositol 4-phosphate (PI4P). Eventually, PI4P is hydrolyzed at the RE, making the exchange cycle irreversible. Thus, OSBP is at the center of a lipid exchange market where a transported cholesterol "costs" a PI4P. Antiviral or anti-cancer molecules target OSBP, suggesting the importance of the OSBP cycle in different physiopathological contexts. The general principles of this cycle are shared by other lipid-transfer proteins., (© 2020 médecine/sciences – Inserm.)

Eukaryotic epithelial cells form a sheet of contiguous cells, called epithelium, by means of the establishment of well-developed junctional complexes. These junctional complexes ensure the cell cohesion in the tissue and separate the plasma membrane into an apical and a basolateral compartment. This apicobasal polarity, which is crucial for both the architecture and the function of epithelia, is mainly maintained by tight junctions (TJS). Indeed, TJS weakening or loss disrupts the integrity of the epithelium, a process participating to the formation and progression of carcinomas. It has recently been shown that TRAF4, a protein dynamically localized in TJS and commonly overexpressed in carcinomas, plays a variety of functions in tumor progression. Here, we review recent data implicating TRAF4 in carcinogenesis. First, the conserved TRAF proteins family will be presented, and then the molecular mechanism addressing TRAF4 to TJS which involves lipid binding by the TRAF domain will be described. The various roles of TRAF4 in carcinogenesis will be discussed. Finally, we will highlight the ability of all TRAF proteins to bind lipids and discuss its potential functional relevance., (© Société de Biologie, 2015.)