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NINDSNIMHNICHDNIDCDNEINIDCRNIANIAAANIDANHGRI NCCIHNIDDKNIEHSCCB

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NIH Distinguished Investigator

Juan S Bonifacino, Ph.D.

Section on Intracellular Protein Trafficking

Cell Biology and Neurobiology Branch, NICHD
Building 35 Room 2F-226
35A Convent Drive MSC 3758 MSC3758
Bethesda MD 20892-3758
Office: 301-496-6368

Fax: 301-402-9319
bonifacinoj@helix.nih.gov

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



Our laboratory investigates the molecular mechanisms by which transmembrane proteins (referred to as “cargo”) are sorted to different compartments of the endomembrane system in eukaryotic cells. This system comprises 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 platelet dense bodies), and different 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 our 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. Knowledge gained from this research is applied to the elucidation of disease mechanisms, including congenital disorders of protein traffic such as the pigmentation and bleeding disorder Hermansky-Pudlak syndrome (HPS) and the neurocutaneous disorder MEDNIK syndrome.

In recent work, we found that interaction of sorting signals contained within the cytosolic tails of various transmembrane receptors with the adaptor protein 1 (AP-1) complex at the TGN and/or endosomes mediates sorting of the receptors to the somatodendritic domain of hippocampal neurons. Sorting involves selective packaging into somatodendritic transport carriers, which are segregated from axonal transport carriers at a pre-axonal exclusion zone (PAEZ) in the axon hillock through differential association with distinct microtubule motors. We also discovered a novel complex named BORC that promotes centrifugal transport of lysosomes and late endosomes, and another novel complex named EARP that mediates recycling of internalized receptors to the cell surface, in both neuronal and non-neuronal cells.

Staff Image
  • Dylan Britt, B.S.
    Post baccalaureate Student

  • Yu Chen, Ph.D.
    Research Fellow

  • Ginny Farias, Ph.D.
    Postdoctoral Fellow

  • David Gershlick, Ph.D.
    Postdoctoral Fellow

  • Carlos Guardia, Ph.D.
    Postdoctoral Fellow

  • Rui Jia, Ph.D.
    Postdoctoral Fellow

  • Tal Keren-Kaplan, Ph.D.
    Postdoctoral Fellow

  • Rafael Mattera, Ph.D.
    Staff Scientist

  • Jing Pu, Ph.D.
    Postdoctoral Fellow

  • Sang Yoon Park, Ph.D.
    Postdoctoral Fellow

  • Xiaolin Zhu, DNP, CRNP, Lt, USPHS
    Technician

  • 1) Jain S, Farías GG and Bonifacino JS (2015)
  • Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1
  • Mol. Biol. Cell. , 26, 218-228
  • 2) 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
  • 3) 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
  • 4) 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
  • 5) Ren X, Park SY, Bonifacino JS* and Hurley JH* (2014)
  • How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4
  • eLife, 3:e01754 . (*co-corresponding authors)
  • 6) Mattera R, Farías GG, Mardones GA and Bonifacino JS (2014)
  • Co-assembly of Viral Envelope Glycoproteins Regulates their Polarized Sorting in Neurons
  • PLoS Path. 10:e1004107
  • 7) Ren X, Farías GG, Canagarajah BJ, Bonifacino JS* and Hurley JH* (2013)
  • Structural basis for recruitment and activation of the AP-1 clathrin adaptor complex by Arf1
  • Cell, 152, 755-767. (*co-corresponding authors)
  • 8) Zhang ZR, Bonifacino JS and Hegde R (2013)
  • Deubiquitinases sharpen substrate discrimination during membrane protein degradation from the ER
  • Cell , 154, 609-622
  • 9) Guo X, Mattera R, Ren X, Chen Y, Retamal C, González A and Bonifacino JS (2013)
  • The Adaptor Protein-1 mu1B subunit expands the repertoire of basolateral sorting signal recognition in epithelial cells
  • Dev. Cell. , 27, 353-366
  • 10) Prabhu Y, Burgos PV, Schindler C, Farías G, Magadán JG and Bonifacino JS (2012)
  • Adaptor protein-2-mediated endocytosis of the gamma-secretase BACE1 is dispensable for amyloid precursor protein processing
  • Mol. Biol. Cell, 23, 2339-2351
  • 11) Farías GG, Cuitino L, Guo X, Ren X, Jarnik M, Mattera R and Bonifacino JS (2012)
  • Signal-mediated, AP-1/clathrin-dependent sorting of transmembrane receptors to the somatodendritic domain of hippocampal neurons
  • Neuron , 75, 810-823
  • 12) Burgos PV, Mardones GA, Rojas AL, daSilva LLP, Prabhu Y, Hurley JH and Bonifacino JS (2010)
  • Sorting of the Alzheimer’s Disease Amyloid Precursor Protein mediated by the AP-4 complex
  • Dev. Cell , 18, 425-436
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