Peralta Lab Home Page
The fundamental event in synaptic communication within the brain involves the release of a neurotransmitter by one cell and the binding of this neurotransmitter to specialized receptors on a recipient cell. The activation of neurotransmitter receptors leads to a variety of short and long term biochemical responses that modulate the electrical properties of individual neurons; these alterations in cellular activity eventually culminate in complex phenomena such as learning, memory and behavior. Research within the Peralta lab addresses the molecular mechanisms by which the neurotransmitter acetylcholine regulates cellular responses through the binding of muscarinic acetylcholine receptors. We have succeeded in isolating the genes encoding important components of acetylcholine-regulated signaling pathways including the muscarinic receptors, intermediate transducing proteins (such as G proteins and kinases) and ion channels, the key targets of neuromodulation. Whereas biochemists employ in vitro reconstitution experiments to determine important functional properties of enzymes, we utilize a "cellular" reconstitution approach involving the introduction of genes encoding receptors, transducing proteins and ion channels into model cell systems. Our approach, though decidedly reductionist, allows us to experimentally manipulate complex, electrophysiological signaling pathways at the molecular level. In particular, we have provided the first molecular description of the pathway linking a G protein-coupled receptor to the modulation of a defined potassium channel. This work has yielded novel insights into the role of protein phosphorylation and potassium channel regulation and has provided the first direct evidence that tyrosine kinases modulate ion channel activity. Moreover, our studies have lead to specific, testable predictions about the mechanisms by which receptors modulate defined ion channels in normal neurons. By exploring the pathways linking neurotransmitters to particular cellular responses, we expect to provide relevant insights into neighboring areas of research concerned with information processing among arrays of neurons.
Selected Publications:
Carroll, R. C., Morielli, A.D., Peralta, E. (1995). Enhancement of m4 muscarinic acetylcholine receptor-induced calcium release: coincidence detection at the level of phospholipase C signalling. Curr. Biol. 5:536-544.
Kunkel, M.T., Peralta, E.G. (1995). Identification of domains conferring G protein regulation on inward rectifier potassium channels. Cell 83:443-449.
Hunt, T.W., Fields, T.A., Casey, P.J., Peralta, E.G. RGS10, is a selective activator of Gai GTPase activity (1996). Nature 383:175-177.