Juan S. Bonifacino, Ph.D.
NIH Distinguished Investigator
Section on Intracellular Protein Trafficking
Building 35A, Room 2F-226
9000 Rockville Pike
Bethesda, MD 20892
Protein Sorting in the Endosomal-Lysosomal System
We investigate the molecular mechanisms by which transmembrane proteins are sorted to different compartments of the endomembrane system such as endosomes, lysosomes, and a group of cell type–specific organelles known as lysosome-related organelles (e.g., melanosomes and platelet dense bodies). Sorting is mediated by recognition of signals present in the cytosolic domains of the transmembrane proteins by adaptor proteins that are components of membrane coats (e.g., clathrin coats). Among these adaptor proteins are the heterotetrameric AP-1, AP-2, AP-3, and AP-4 complexes, the monomeric GGA proteins, and the heteropentameric retromer complex. Proper sorting requires the function of additional components of the trafficking machinery that mediate vesicle tethering and fusion. Current work in our laboratory is aimed at elucidating the structure, regulation, and physiological roles of coat proteins and vesicle-tethering factors and investigating human diseases that result from genetic defects (e.g., Hermansky-Pudlak syndrome and neurodegenerative and neurodevelopmental disorders) in these proteins.
Burgos PV, Mardones GA, Rojas AL, daSilva LL, Prabhu Y, Hurley JH, Bonifacino JS. Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex. Dev Cell. 2010;18(3):425-36.
Pérez-Victoria FJ, Schindler C, Magadán JG, Mardones GA, Delevoye C, Romao M, Raposo G, Bonifacino JS. Ang2/fat-free is a conserved subunit of the Golgi-associated retrograde protein complex. Mol Biol Cell. 2010;21(19):3386-95.
Magadán JG, Pérez-Victoria FJ, Sougrat R, Ye Y, Strebel K, Bonifacino JS. Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps. PLoS Pathog. 2010;6(4):e1000869.
Ishikura S, Weissman AM, Bonifacino JS. Serine residues in the cytosolic tail of the T-cell antigen receptor alpha-chain mediate ubiquitination and endoplasmic reticulum-associated degradation of the unassembled protein. J Biol Chem. 2010;285(31):23916-24.
Mattera R, Boehm M, Chaudhuri R, Prabhu Y, Bonifacino JS. Conservation and diversification of dileucine signal recognition by adaptor protein (AP) complex variants. J Biol Chem. 2011;286(3):2022-30.