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 synaptic transmission are thought to be the basis for higher cognitive processes such as learning and memory.

In the last decade, a number of key proteins involved in exocytosis have been identified. Many of these proteins are members of highly conserved protein families required for general intracellular membrane trafficking, yet their precise roles in synaptic transmission remain unclear. Three essential proteins, called the SNARE proteins (for SNAP receptors), are thought to mediate the vesicle fusion step. Two proteins, UNC-13 (Munc13) and UNC-18(Munc18) are also essential for release, where as tomosyn (TOM-1) is thought to negatively regulate secretion. All three proteins are known to physically interact with the SNARE protein syntaxin. A major focus of my research in the next few years is to characterize the role of these proteins in synaptic exocytosis and to explore their sequential involvement relative to SNARE complex formation. In addition, we are interested in the molecular mechanisms that determine synaptic organization, with present emphasis on the signals that govern post-synaptic receptor localization.

In my laboratory, we combine genetic and molecular approaches with EM and in vivo electrophysiological analysis of synapses to study the involvement of proteins in exocytosis using the nematode Caenorhabditis elegans. This is a powerful genetic model organism in which to study synaptic function. First, C. elegans mutants disrupting synaptic transmission are easily identified and often viable. Second, the entire genomic sequence of C. elegans is known. Third, proteins required for synaptic transmission in C. elegans are highly conserved across species. Fourth, we can examine relevant mutants electrophysiologically and ultrastructurally, permitting detailed functional analysis.

Representative Publications

EO Gracheva, AO Burdina, D Touroutine, M Berthelot-Grosjean, H Parekh and JE Richmond (2007) Tomosyn negatively regulates CAPS-dependent peptide release at Caenorhabditis elegans synapses. J Neurosci 27: 10176-84.

EO Gracheva, AO Burdina, AM Holgado, M Berthelot-Grosjean, G Hadwiger, ML Nonet, RM Weimer and JE Richmond (2006) Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans. PLoS Biology Vol 4:1426-37.

RM Weimer, EO Gracheva, O Meyrignac, KG Miller, JE Richmond and JL Bessereau (2006) UNC-13 and UNC-10/rim localize synaptic vesicles to specific membrane domains. J Neurosci 26: 8040-7

D Touroutine, RM Fox, SE Von Stetina, A Burdina, DM Miller III and JE Richmond (2005) ACR-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the C. elegans neuromuscular junction. J. Biol. Chem. 280: 27013-21.

C Gally, S Eimer, JE Richmond and JL Bessereau (2004) A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans. Nature 431: 578-82.

JE Richmond, RM Weimer and EM Jorgensen (2001) An open form of syntaxin bypasses the requirement for UNC-13 in synaptic transmission. Nature 412: 338-41.

JE Richmond, WS Davis and EM Jorgensen (1999) UNC-13 is required for synaptic vesicle fusion in C. elegans. Nature Neuroscience 2: 959-64.