IMIM and CEXS-UPF: New role of cholesterol in regulating brain proteins discovered

IMIM and CEXS-UPF: New role of cholesterol in regulating brain proteins discovered

News from IMIM and CEXS-UPF

A study led by researchers at the IMIM and the Institute of Medical Physics and Biophysics at the Faculty of Medicine in Charité Hospital, Berlin, published in Nature Communications, demonstrates that the cholesterol present in cell membranes can interfere with the function of an important brain membrane protein, through a previously unknown mode of interaction. Specifically, cholesterol is capable of regulating the activity of the adenosine receptor, by invading it and accessing the active site. This will allow new ways of interacting with these proteins to be devised that in the future could lead to drugs for treating diseases like Alzheimer's.

The adenosine receptor belongs to the GPCR family (G Protein-Coupled Receptors), a large group of proteins located in cell membranes, which are key in the transmission of signals and communication between cells.

"Cholesterol is an essential component of neuronal membranes, where GPCRs reside along with other proteins. Interestingly, the levels of cholesterol in the membrane are altered in diseases such as Alzheimer's, where GPCRs like the adenosine receptor play a key role", explains Jana Selent, head of the GPCR Drug Discovery research group at the GRIB (IMIM-UPF). "This study has shown that cholesterol can exert direct action on this important family of proteins in neuronal membranes, the GPCRs, and establishes the basis for a hitherto unknown interaction pathway between the cell membrane and proteins", adds the researcher.

More information:
IMIM website and CEXS-UPF website

Reference article:
Guixà-González R, Albasanz JL, Rodríguez-Epigares I, Pastor M, Sanz F, Martí-Solano M, Manna M, Martínez-Seara H, Hildebrand PW, Martí M, Selent J. Membrane cholesterol access into a G-protein-coupled receptor. NatureCommunications, 8:14505, 2017. (DOI: doi:10.1038/ncomms14505)