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Juan S. Bonifacino, Ph.D.

Senior Investigator
NICHD
Section on Intracellular Protein Trafficking
Building 18T
18T Center Drive
Bethesda, MD 20892
301-496-6368

Research Topics

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.

Biography

Dr. Juan Bonifacino received his doctoral degree in biochemistry from the University of Buenos Aires, Argentina, in 1981. He then moved to the NIH, where he pursued postdoctoral studies with Dr. Richard D. Klausner. He rose through the ranks, eventually becoming the Head of the Cell Biology and Metabolism Program. In 2008, he was appointed NIH Distinguished Investigator. Since the early 1990s, Dr. Bonifacino's group has conducted research on signals and adaptor proteins that mediate protein sorting to endosomes and lysosomes. His group discovered new sorting signals and adaptor proteins, and applied this knowledge to the elucidation of the causes of various human diseases including the Hermansky-Pudlak syndrome type 2 and autosomal dominant polycystic liver disease. Dr. Bonifacino has served in various editorial capacities for journals including Developmental Cell, Molecular Cell, Molecular Biology of the Cell, Journal of Cell Biology, Journal of Biological Chemistry and Traffic. He is also the co-editor of the books Current Protocols in Cell Biology and Short Protocols in Cell Biology. He has served as a member of the Council of the American Society for Cell Biology and chaired various scientific conferences. He has delivered the Alex Novikoff, Leonardo Satz, George Connell and G. Burroughs Mider lectures, and is an Honorary Professor of Biological Chemistry at the University of Buenos Aires and a Sackler Lecturer at Tel Aviv University, Israel. His lab has trained over 70 postdoctoral fellows and students, most of whom have pursued careers in academic research.

Selected Publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
This page was last updated on October 18th, 2011