FACULTY RESEARCH

Faculty List

Cameron Gundersen, Ph.D.

Work Email Address: cgundersen@mednet.ucla.edu

Lab Number: (310) 825-6639

Work Phone Number: 310-825-3423

Office Address:
63-170C CHS
Los Angeles, CA 90095

Department / Division Affiliations
Professor, Molecular & Medical Pharmacology
Member, Brain Research Institute, Neuroscience GPB Home Area

Research Interests
The principal focus of our research is to understand the mechanism of transmitter release at nerve endings. We are approaching this problem from the vantage point of a family of secretory vesicle proteins, the cysteine string proteins (csps). Csps appear to be expressed in all cells that, like neurons, display regulated secretion. Current evidence suggests that csps are dual function proteins. First, we have proposed that csps participate in an interaction with presynaptic calcium (Ca) channels which ensures that only those Ca channels with a synaptic vesicle docked nearby open in response to an action potential. Second, we have hypothesized that csps play a direct role in the membrane fusion event itself. Evidence for the first hypothesis comes from studies of csp mutant fruit flies, which display a temperature-dependent deficit of neurotransmitter release. This reduction of transmitter release is correlated with a decline in the presynaptic entry of Ca ions that normally occurs in response to nerve stimulation. Part of our ongoing work is aimed at understanding the biochemical and biophysical mechanism of the csp/Ca channel interaction. The idea that csps are directly involved in membrane fusion evolved from the discovery that virtually all of the dozen (or more) cysteine residues of the cysteine string domain are fatty acylated. This fatty acylation creates a region of unprecedented hydrophobicity that is uniquely suited to mediate fusion events at membrane interfaces (like those that occur at the contact between secretory organelles and the plasma membrane). A major focus of our work is to investigate further the role of csps (and other csp-like proteins) in membrane fusion.As part of these efforts, we recently became interested in the role of unconventional myosins in regulated exocytosis. Our model for csp's role in membrane fusion depends on the involvement of a motor protein, so we are very interested in the possible interaction between csp and myosin. In addition to these basic interests in csps, we recently initiated studies of the mechanism by which lithium (Li) ions (and other agents that are used to treat manic-depressive disorders) alter neuronal function. This work emerged from the discovery that therapeutically relevant concentrations of Li enhance csp gene expression in rat brain in vivo, as well as in PC12 cells in vitro. We are pursuing this work by trying to understand the functional consequences of up-regulating csp expression, as well as the mechanism by which lithium influences gene expression. Ideally, this work will shed light on the cause and improved treatment of these disorders.


Publications
Cordeiro, ML Gundersen, CB Umbach, JA Convergent effects of lithium and valproate on the expression of proteins associated with large dense core vesicles in NGF-differentiated PC12 cells. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. . 2004; 29(1): 39-44.
Kohan, SA Gundersen, CB Protein synthesis is required for the transition to Ca(2+)-dependent regulated secretion in progesterone-matured Xenopus oocytes. Journal of experimental zoology. Part A, Comparative experimental biology. . 2003; 300(2): 113-25.
Cordeiro, ML Gundersen, CB Umbach, JA Dietary lithium induces regional increases of mRNA encoding cysteine string protein in rat brain. Journal of neuroscience research. . 2003; 73(6): 865-9.
Cordeiro, ML Gundersen, CB Umbach, JA Lithium ions modulate the expression of VMAT2 in rat brain. Brain research. . 2002; 953(1-2): 189-94.
Mischel,PS, Umbach, JA, Eskandari,S, Smith, SG, Gundersen, CB, Zampighi, GA Nerve growth factor signals via pre-existing TrkA receptor monomers. Biophysical Journal 2002; 83: .
Gundersen, CB, Kohan, SA, ChenQ, Iagnemma,J, Umbach, JA Protein kinase C eta triggers cortical granule exocytosis in Xenopus oocytes. Journal of Cell Science 2002; 115: 1313-1320.
Saitoe, M Schwarz, TL Umbach, JA Gundersen, CB Kidokoro, Y Absence of junctional glutamate receptor clusters in Drosophila mutants lacking spontaneous transmitter release. Science. . 2001; 293(5529): 514-7.
Gundersen, CB Aguado, F Sou, S Mastrogiacomo, A Coppola, T Kornblum, HI Umbach, JA Cysteine string proteins are associated with cortical granules of Xenopus laevis oocytes. Cell and tissue research. . 2001; 303(2): 211-9.
Cordeiro, ML Umbach, JA Gundersen, CB Lithium ions Up-regulate mRNAs encoding dense-core vesicle proteins in nerve growth factor-differentiated PC12 cells. Journal of neurochemistry. . 2000; 75(6): 2622-5.
Cordeiro, ML Umbach, JA Gundersen, CB Lithium ions enhance cysteine string protein gene expression in vivo and in vitro. Journal of neurochemistry. . 2000; 74(6): 2365-72.
Poage, RE Meriney, SD Gundersen, CB Umbach, JA Antibodies against cysteine string proteins inhibit evoked neurotransmitter release at Xenopus neuromuscular junctions. Journal of neurophysiology. . 1999; 82(1): 50-9.
Mastrogiacomo,A, Kornblum,HI, Umbach,JA & Gundersen, CB A Xenopus cysteine string protein with a cysteine residue in the J-domain. Biochim. Biophys. Acta 1998; 1401: 239-241.
Whitelegge, JP Gundersen, CB Faull, KF Electrospray-ionization mass spectrometry of intact intrinsic membrane proteins. Protein science : a publication of the Protein Society. . 1998; 7(6): 1423-30.
Umbach, JA Saitoe, M Kidokoro, Y Gundersen, CB Attenuated influx of calcium ions at nerve endings of csp and shibire mutant Drosophila. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 1998; 18(9): 3233-40.
Umbach, JA Gundersen, CB Evidence that cysteine string proteins regulate an early step in the Ca2+-dependent secretion of neurotransmitter at Drosophila neuromuscular junctions. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 1997; 17(19): 7203-9.
Coppola, T Gundersen, C Widespread expression of human cysteine string proteins. FEBS letters. . 1996; 391(3): 269-72.
Kohan, SA Pescatori, M Brecha, NC Mastrogiacomo, A Umbach, JA Gundersen, CB Cysteine string protein immunoreactivity in the nervous system and adrenal gland of rat. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 1995; 15(9): 6230-8.
Gundersen, CB Mastrogiacomo, A Umbach, JA Cysteine-string proteins as templates for membrane fusion: models of synaptic vesicle exocytosis. Journal of theoretical biology. . 1995; 172(3): 269-77.
Mastrogiacomo, A Gundersen, CB The nucleotide and deduced amino acid sequence of a rat cysteine string protein. Brain research. Molecular brain research. . 1995; 28(1): 12-8.
Umbach, JA Zinsmaier, KE Eberle, KK Buchner, E Benzer, S Gundersen, CB Presynaptic dysfunction in Drosophila csp mutants. Neuron. . 1994; 13(4): 899-907.
Gundersen, CB Mastrogiacomo, A Faull, K Umbach, JA Extensive lipidation of a Torpedo cysteine string protein. The Journal of biological chemistry. . 1994; 269(30): 19197-9.
Mastrogiacomo, A Parsons, SM Zampighi, GA Jenden, DJ Umbach, JA Gundersen, CB Cysteine string proteins: a potential link between synaptic vesicles and presynaptic Ca2+ channels. Science. . 1994; 263(5149): 981-2.
Gundersen, C.B. and J.A. Umbach Suppression cloning of the cDNA for a candidate subunit of a presynaptic calcium channel. Neuron 1992; 9: 527-537.