TITLE: Membrane fusion mediated by SNARE proteins
AUTHOR: Reinhard Jahn, Ph.D., Max Planck Institute for Biophysical Chemistry
TIME: 12:00:00 PM DATE: Monday, March 23, 2015
PLACE: Porter Neuroscience Research Center
Live NIH Videocast (archived after seminar)
Director, Department of Neurobiology
Major Research Interests
Our group is interested in the mechanisms of membrane fusion, with the main emphasis on regulated exocytosis in neurons. Intracellular membrane fusion events are mediated by a set of conserved membrane proteins, termed SNAREs. For fusion to occur, complementary sets of SNAREs need to be present on both of the fusing membranes, which then assemble in a zipper-like fashion to initiate membrane merger. The neuronal SNAREs are among the best characterized. They are the targets of the toxins responsible for botulism and tetanus, and they are regulated by several addtional proteins including synaptotagmin, the calcium sensor for neurotransmitter release. To understand how these proteins mediate fusion, we study their properties in vitro with biochemical and biophysical approaches using native and artificial membranes.
In a second set of projects, we use modern techniques such as quantitative proteomics to better understand supramolecular protein complexes involved in synaptic function. Using our quantitative description of synaptic vesicles as point of departure we aim at unraveling presynaptic protein networks involved in synaptic vesicle docking and fusion. Furthermore, we are studying regulation of presynaptic function by small GTPases and by protein phosphorylation.
Selected Recent Publications
- Honigmann A, van den Bogaart G, Iraheta E, Risselada JH, Milovanovic D, Mueller V, Muellar S, Diederichsen U, Fasshauer D, Grubmüller H, Hell SW, Eggeling C, Kühnel K, Jahn R (2013) Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment. Nature Struct Mol Biol 20, 679–686
- Park Y, Hernandez JM, van den Bogaart G, Ahmed S, Holt M, Riedel D, Jahn R (2012) Controlling synaptotagmin activity by electrostatic screening. Nature Struct Mol Biol 19, 991-997
- Jahn R, Fasshauer D (2012) Exocytosis of synaptic vesicles – molecular machines, calcium, and beyond (review). Nature, 490(7419):201-7
- Hernandez JM, Stein A, Behrmann E, Riedel D, Cypionka A, Farsi Z, Walla PJ, Raunser S, Jahn R (2012) Membrane fusion intermediates via directional and full assembly of the SNARE complex. Science 336, 1581-1584
- Chua JJ, Butkevich E, Worseck JM, Kittelmann M, Gronborg M, Behrmann E, Stelzl U, Pavlos NJ, Lalowski M, Eimer S, Wanker EE, Klopfenstein DR*, Jahn R* (2012) Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter. Proc Natl Acad Sci USA 109, 5862-5867
- van den Bogaart G, Meyenberg K, Risselada JH, Amin H, Willig KI, Hubrich BE, Dier M, Hell SW, Grubmüller H, Diederichsen U, Jahn R (2011) Membrane protein sequestering by ionic protein-lipid interactions. Nature 479, 552-555
- van den Bogaart G, Thutupalli S, Risselada JH, Meyenberg K, Holt M, Riedel D, Diederichsen U, Herminghaus S, Grubmüller H, Jahn R (2011) Synaptotagmin-1 may be a distance regulator acting upstream of SNARE nucleation. Nat Struct Mol Biol 18, 805-812
- Stein A, Weber G, Wahl MC, Jahn R (2009) Helical extension of the neuronal SNARE complex into the membrane. Nature 460, 525-528
About the Seminars
The NIH Neuroscience Seminar Series features lectures and discussions with leading neuroscientists. Sponsored byNINDS, NIMH, NIA, NIDCD, NIDA, NICHD, NEI, NIAAA,NIDCR, NHGRI and NCCIH, this year’s series offers seminars on aspects of molecular, cellular, developmental and cognitive neuroscience as well as neuroscience related topics in disease, pain and genetics. Seminars are held on the NIH campus on Mondays at noon in the Porter Neuroscience Research Center, Room 620/630, Building 35.