Prof Juan S BONIFACINO
Head of Cell Biology and Metabolism Program, NIH, Fogarty International Center
Associate editor of Developmental Cell
Editor of Current Protocols in Cell Biology
Council of the American Society for Cell Biology
Head, Cell Biology and Metabolism Program
National Institute of Child Health and Human Development
National Institutes of Health, Bethesda, MD
Expertise: Cell Biology and Protein Trafficking and Disease in Animal Cells
Dr. Bonifacino received his Ph.D. in Biochemistry from the University of Buenos Aires, Argentina. He was a post-doctoral fellow in the laboratory of Richard D. Klausner at NIDDK and NICHD, studying the mechanisms of assembly and quality control of multi-protein complexes in the endoplasmic reticulum. He rose through the ranks to his current position as Head of the Section on Intracellular Protein Trafficking, and Associate Scientific Director of the Cell Biology and Neurobiology Branch, NICHD. His laboratory investigates the molecular mechanisms by which proteins are delivered to different intracellular compartments and the diseases that result from dysfunction of these mechanisms. Specific projects include the study of the mechanisms of polarized sorting in neurons, coat proteins involved intracellular transport, organelle positioning and motility, and endosomal retrieval pathways mediated by retromer and tethering complexes.
Dr. Juan Bonifacino investigate the molecular mechanisms by which transmembrane proteins (referred to as cargo) are sorted to different compartments of the endomembrane system in eukaryotic cells. The system consists of an array of membrane-enclosed organelles including the endoplasmic reticulum (ER), the Golgi apparatus, the trans-Golgi network (TGN), endosomes, lysosomes, lysosome-related organelles (LROs) (e.g., melanosomes), and various domains of the plasma membrane in polarized cells (e.g., epithelial cells and neurons). Transport of cargo between these compartments is mediated by carrier vesicles or tubules that bud from a donor compartment, translocate through the cytoplasm, and eventually fuse with an acceptor compartment. Work in his laboratory focuses on the molecular machineries that mediate these processes, including (1) sorting signals and adaptor proteins that select cargo proteins for packaging into the transport carriers, (2) microtubule motors that drive movement of the transport carriers and other organelles through the cytoplasm, and (3) tethering factors that promote fusion of the transport carriers to acceptor compartments. They study these machineries in the context of different intracellular transport pathways, including endocytosis, recycling to the plasma membrane, retrograde transport from endosomes to the TGN, biogenesis of lysosomes and LROs, and polarized sorting in epithelial cells and neurons. They apply knowledge gained from this research to the elucidation of disease protein trafficking diseases such as the pigmentation and bleeding disorder Hermansky-Pudlak syndrome (HPS) and the neuro-cutaneous disorder MEDNIK syndrome. In addition, they study how the molecular mechanisms of protein transport are exploited by intracellular pathogens such as HIV-1.
List of Key Publications :
1. Bonifacino JS and Neefjes J (2017) Moving and positioning the endolysosomal system. Curr Opin Cell Biol 47:1-8
2. Farías GG, Guardia CM, De Pace R, Britt DJ and Bonifacino JS (2017) BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon. PNAS 114(14):E2955-E2964
3. Farías GG, Guardia CM, Britt DJ, Guo X and Bonifacino JS (2015) Sorting of dendritic and axonal vesicles at the pre-axonal exclusion zone. Cell Reports 13,1221-1232
4. Pu J, Schindler C, Jia R, Jarnik M, Backlund P and Bonifacino JS (2015) BORC, a multisubunit complex that regulates lysosome positioning. Dev. Cell 33, 176-188.
5. Schindler C, Chen Y, Pu J, Guo X and Bonifacino JS (2015) EARP is a multisubunit tethering complex involved in endocytic recycling. Nat. Cell Biol. 17, 639-650.