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.
Farías GG, Cuitino L, Guo X, Ren X, Jarnik M, Mattera R, Bonifacino JS. Signal-mediated, AP-1/clathrin-dependent sorting of transmembrane receptors to the somatodendritic domain of hippocampal neurons. Neuron. 2012;75(5):810-23.
Schindler C, Chen Y, Pu J, Guo X, Bonifacino JS. EARP is a multisubunit tethering complex involved in endocytic recycling. Nat Cell Biol. 2015;17(5):639-50.
Mattera R, Farías GG, Mardones GA, Bonifacino JS. Co-assembly of viral envelope glycoproteins regulates their polarized sorting in neurons. PLoS Pathog. 2014;10(5):e1004107.
Pu J, Schindler C, Jia R, Jarnik M, Backlund P, Bonifacino JS. BORC, a multisubunit complex that regulates lysosome positioning. Dev Cell. 2015;33(2):176-88.
Jain S, Farías GG, Bonifacino JS. Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1. Mol Biol Cell. 2015;26(2):218-28.