Dr. Richmond's Research
Synaptic transmission is the principal form of rapid communication between neurons. In this calcium-regulated process, synaptic vesicles are triggered to fuse with the presynaptic membrane at specialized active zones. Vesicle fusion releases neurotransmitter that binds to and activates post-synaptic receptors. Changes in the strength of this signaling process are thought to be important for learning and memory.
In my laboratory, we combine genetic and molecular approaches with high-pressure freeze EM, optogenetics and in vivo electrophysiological analyses of synapses to study the involvement of proteins in exocytosis and endocytosis using the nematode Caenorhabditis elegans and more recently Drosophila. These are powerful genetic model organisms, in which we use the accessibility of the neuromuscular junctions in wild type and mutated animals as a tractable model synapse to address the following questions.
Three conserved SNARE proteins (for SNAP receptors) are known to be essential for synaptic vesicle fusion. My lab is interested in how other SNARE- interacting proteins function in the regulation of synaptic transmission. We have shown that both UNC-13 (Munc13) and UNC-18(Munc18) play essential roles in the priming of vesicles for fusion, where as tomosyn negatively regulates this process. Furthermore, our research has demonstrated an important role for tomosyn in PKA-dependent learning. We are presently extending these studies to determine the signaling pathway and mechanism by which tomosyn impacts this conserved form of synaptic plasticity.
In addition, we are interested in the molecular mechanisms that determine presynaptic organization, with present emphasis on the signals that govern the docking of synaptic vesicles at the presynaptic density, as well as the events underlying synaptic remodeling.
No synapse can function effectively without the proper placement of post-synaptic receptors. In C. elegans
, three receptor classes (2ACh and 1GABA) are localized to specific post-synaptic densities at neuromuscular junctions, via different molecular scaffolds. The lab is actively engaged in identifying the components responsible for the trafficking and localization of both ACh receptors.
Szi-Chieh Yu, Susan M. Klosterman, Ashley A. Martin, Elena O. Gracheva, Janet E. Richmond (2013) Differential Roles for Snapin and Synaptotagmin in the Synaptic Vesicle Cycle. PloS One February 2013:8(2):e57842.
Kaiyun Chen, Antje Richlitzki, David E. Featherstone, Martin Schwärzel, and Janet E. Richmond (2011) Tomosyn-dependent regulation of synaptic transmission is required for a late phase of associative odor memory. Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18482-7.
Sancar F, Touroutine D, Gao S, Oh HJ, Gendrel M, Bessereau JL, Kim H, Zhen M, Richmond JE (2011) The dystrophin-associated protein complex maintains muscle excitability by regulating BK channel localization. JBC 286(38): 33501-10.
Richmond J (2009). Dissecting and Recording from The C. Elegans Neuromuscular Junction. JoVE. Feb 27( 24) pii=1165, doi: 10.3791/1165
Gracheva EO, Burdina AO, Touroutine D, Berthelot-Grosjean M, Parekh H, Richmond JE (2007) Tomosyn negatively regulates CAPS-dependent peptide release at Caenorhabditis elegans synapses. J Neurosci 27(38): 10176-84.
Gracheva EO, Burdina AO, Holgado AM, Berthelot-Grosjean M, Ackley BD, Hadwiger G, Nonet ML, Weimer RM, Richmond JE (2006) Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans. PLoS Biology 4: 1426-37.
Touroutine D, Fox RM, Von Stetina SE, Burdina A, Miller III DM, Richmond JE (2005) ACR-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the C. elegans neuromuscular junction. JBC 280(29): 27013-21.