Erik Jorgensen
Professor of Biology
B.S. University of California, Berkeley
Ph.D. University of Washington
Erik Jorgensen's Lab Page
Erik Jorgensen's PubMed Literature Search
Erik Jorgensen's Howard Hughes Medical Institute Page
Research
What is the molecular nature of memory? It seems that memory is encoded by changes in the strength of synapses. It is our goal to identify the molecules that function at the synapse and to understand how the activities of these molecules are changed to strengthen or weaken a synapse. To identify such molecules we have undertaken a genetic analysis of neurotransmission in the nematode Caenorhabditis elegans. C. elegans is particularly advantageous for genetic studies of the nervous system for several reasons: First, mutants with defective synapses are viable and can be studied as adults. Second, we can select for mutants with defective neurotransmission using drug resistance screens. Third, we can characterize mutant synapses at the ultrastructural and electrophysiological level. Fourth, the entire genomic sequence of the nematode has been completed; and knockouts of many genes have been generated; this greatly expedites the characterization of genes.
Our goal is to identify the genes required for synaptic function. Such genes are likely to regulate synaptic vesicle dynamics. When a neuron fires an action potential, calcium ions flow into the axonal terminus of the presynaptic cell. Calcium influx causes synaptic vesicles to fuse with the plasma membrane and to release neurotransmitter to the surface of the neighboring cell.
What is the molecular mechanism of vesicle fusion? In our screens we have identified UNC-13, UNC-18 and the SNARE proteins. We are characterizing the molecular interactions that drive fusion. Using electrophysiological recordings and analysis of vesicles by electron microscopy we have determined that these proteins are required for docking and priming vesicles for release at the cell membrane.
What are the molecular mechanisms of synaptic vesicle retrieval? Once synaptic vesicles have fused with the plasma membrane, the components must be retrieved from the plasma membrane via endocytosis to regenerate a reserve pool of vesicles. We are studying clathrin-mediated endocytosis and lipid modifying proteins that are essential for endocytosis.
What are the mechanisms for synaptic plasticity? We are currently studying the role of GTPases in potentiating or weakening synaptic strength. Our data indicate that Gq subunits of trimeric G proteins have novel targets beyond the lipid modifying enzymes of the canonical pathway.
What neurotransmitters function at synapses? GABA is the primary inhibitory neurotransmitter in vertebrate and invertebrate nervous systems. Our analysis of GABA has demonstrated that GABA is an excitatory neurotransmitter at both neurons and muscles in the nematode. Moreover, we have discovered that protons can act as a transmitter at some synapses. These studies suggest that there is an unforeseen richness to the molecular complexity of the nervous system – and hence the brain.
References
1. Ernstrom G, RM Weimer, D Greenstein, EM Jorgensen (2012) The V-ATPase subunit B is required for synaptic vesicle acidification and locomotion in Caenorhabditis elegans. Genetics, (Mar 28)
2. Frøkjær-Jensen C, MW Davis, M Ailion, EM Jorgensen (2012) Improved Mos1-mediated transgenesis in C. elegans. Nature Methods, 9:117-118
3. Hobson RJ, Liu Q, Watanabe S, and Jorgensen EM (2011) Complexin maintains vesicles in the primed state in C. elegans. Current Biology, 21:106-113
4. Watanabe S, Punge A, Hollopeter G, Willig KI, Hobson RJ, Davis MW, Hell SW , and Jorgensen EM (2011) Protein localization in electron micrographs using fluorescence nanoscopy. Nature Methods, 8:80-84
5. Frøkjær-Jensen C, Davis MW, Hollopeter G, Taylor J, Harris T, Nix P, Lofgren R, Bastiani M, Moerman DG, Jorgensen EM (2010) Targeted gene deletions in C. elegans. Nature Methods, 7(6):451-3
6. Liu Q, Hollopeter G, Jorgensen EM (2009) Graded synaptic transmission at the Caenorhabditis elegans neuromuscular junction. Proc Natl Acad Sci, 106(26):10823-10823
7. Hammarlund M, Nix P, Hauth L, Jorgensen EM, Bastiani MJ (2009) Axon regeneration requires a conserved MAP kinase pathway. Science, 323:802-806
8. Gu M, Schuske K, Watanabe S, Baum P, Garriga G. Jorgensen EM (2008) mu2 adaptin is not essential for synaptic vesicle recycling in C. elegans. Journal of Cell Biology, 183:881-892
9. Frøkjær-Jensen C, Davis MW, Hopkins CE, Newmann B, Thummel JM, Olesen S-P, Grunnet M, Jorgensen EM (2008) Single copy insertion of transgenes in C. elegans. Nature Genetics, 40:1375-1383
10. Hammarlund M, Watanabe S, Schuske K, Jorgensen EM (2008) CAPS and syntaxin dock dense core vesicles to the plasma membrane in neurons. Journal of Cell Biology, 180:483-491
11. Beg AP, Ernstrom G, Nix P, Davis MW, Jorgensen EM (2008) Protons act as a transmitter for muscle contraction in C. elegans. Cell, 132:149-160
Updated 4/11/2012
