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Noreen E. Reist, PhD

Department of Biomedical Sciences
Colorado State University
Fort Collins, CO 80523

Phone: 970-491-5882
Fax: 970-491-7907

Program in Molecular, Cellular and Integrative Neurosciences
Program in Cell and Molecular Biology

PhD, Stanford University
BA, University of California, Berkeley

NE Reist PubMed

Picture of Dr. Reist

Research Interests -- Molecular Dissection of Neurotransmitter Release

A fundamental problem in neurobiology today is understanding how chemical synapses work. Most intercellular communication in the nervous system occurs at chemical synapses and proper functioning of these synapses is required for everything from sensation and movement to learning and memory. During synaptic transmission, vesicles carrying a chemical neurotransmitter must dock at release sites, fuse with the presynaptic membrane upon Ca[2+] influx into the presynaptic terminal, and be recycled back into synaptic vesicles. The research in my laboratory focuses on the molecular and cellular mechanisms involved in these processes. Specifically, we are using molecular, genetic, electrophysiological and ultrastructural techniques to identify and functionally characterize molecules involved in the docking, Ca[2+]-triggered fusion, and subsequent recycling of synaptic vesicles.

Using the genetic system of Drosophila, we can examine the functions of proteins in the living animals by knocking out the protein of interest and testing for deficits. We currently are examining the role of the synaptic vesicle protein, synaptotagmin, which is proposed to be the Ca[2+] sensor that triggers vesicle fusion. Mutants that lack synaptotagmin exhibit severe defects in synaptic transmission and nerve terminal ultrastructure, demonstrating that synaptotagmin is an important regulator of synaptic transmission. However, its specific role within the synaptic vesicle cycle has remained unclear.

Biochemical experiments have shown that synaptotagmin interacts with a number of nerve terminal proteins in vitro also suggesting roles for synaptotagmin in vesicle docking, Ca[2+]-triggered fusion and recycling. Using molecular biology techniques, we have engineered mutations at putatively important sites in the synaptotagmin gene. By expressing the specifically mutated protein in flies that otherwise lack synaptotagmin, we can address the function of individual domains of synaptotagmin in transgenic flies. Since biochemical interactions in vitro do not necessarily reflect physiological interactions in vivo, our genetic dissection of protein function in live animals provides critical information about the mechanisms of synaptic transmission.

Using this approach, we have identified a region within synaptotagmin (the C2B Ca[2+]-binding motif) that is required for Ca[2+]-triggered fusion of synaptic vesicles. Mutations within this domain decrease the apparent Ca[2+] affinity of synaptic transmission without disrupting vesicle recycling or distribution, providing strong support for the hypothesis that synaptotagmin is the Ca[2+] sensor for synaptic transmission. Through studies such as these, we are defining the function of critical components of the synaptic vesicle cycle. Such knowledge is required to understand and treat disease that involve defects in neurotransmitter regulation including mental retardation, depression, schizophrenia, and learning disabilities.

Representative Publications

Striegel AR, Biela LM, Evans CS, Wang Z, Delehoy J, Sutton RB, Chapman ER, Reist NE. 2012. Calcium binding by synaptotagmin's C2A domain is an essential element of the electrostatic switch that triggers synchronous synaptic transmission. J Neurosci 32:1253-1260. [link]

Paddock BE, Wang Z, Biela LM, Chen K, Getzy MD, Striegel A, Richmond JE, Chapman ER, Featherstone DE, Reist NE, 2011. Membrane penetration by synaptotagmin is required for coupling calcium binding to vesicle fusion in vivo. J Neurosci 31:2248-2257 PMID: 21307261. [link]

Loewen CA, Reist NE. 2008. Synaptotagmin: Transducing Ca2+-binding to vesicle fusion.  In: Molecular Mechanisms of Neurotransmitter Release (Wang ZW, ed), pp 107-134. Totowa: Humana Press. [To order this book, visit]

Paddock BE, Striegel A, Hui E, Chapman ER, Reist NE. 2008. Ca2+-dependent, phospholipid-binding residues of synaptotagmin are critical for excitation-secretion coupling.  J Neurosci 28:7458-7466. [link]

Tamura T, Hou J, Reist NE, Kidokoro Y. 2007. Nerve-evoked synchronous release and high K+-induced quantal events are regulated separately by Synaptotagmin I at Drosophila neuromuscular junctions. J Neurophysiol 97:540-549. [link]

Loewen CA, Lee SM, Shin YK, Reist NE. 2006. Synaptotagmin's C2B polylysine motif facilitates a Ca[2+]-independent stage of synaptic vesicle priming in vivo. Molec Biol Cell 17:5211-5226. [link]

Loewen CA, Royer SM, Reist NE. 2006. Drosophila synaptotagmin I null mutants show severe alterations in vesicle populations, but calcium-binding motif mutants do not. J Comp Neurol 496:1-12. [link]

Mackler JM, Drummond JA, Loewen CA, Robinson IM, Reist NE. 2002. The C2B Ca[2+]-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nature 418:340-344. [pdf file]

Loewen CA, Mackler JM, Reist NE. 2001. Drosophila synaptotagmin I null mutants survive to early adulthood. Genesis: J Gen Dev 31:30-36. [link]

Mackler JM, Reist NE. 2001. Mutations in the C[2]B domain of synaptotagmin disrupt synaptic transmission at Drosophila neuromuscular junctions. J Comp Neurol 436:4-16. [link]