Kathleen Beckingham
Professor of Biochemistry and Cell Biology
1. Molecular mechanisms of calcium signaling Calcium undergoes complex, intricate movements within cells in response to external stimuli. These calcium mobilization events change cellular activity as a result of calcium binding to "sensor" proteins which then mediate activation of downstream targets. We are using the fly Drosophila melanogaster to investigate calcium signaling in processes within the whole organism. Currently we are focused on two major aspects of calcium signaling;
i) analysis of developmental processes mediated by the ubiquitous calcium sensor calmodulin and ii) investigation of a new testis-specific calcium sensor protein which we have identified and termed Androcam. The sophisticated genetic methodologies available in Drosophila provide unique opportunities for these functional studies. 2. Molecular mechanisms of gravitational sensing Little is understood of the mechanisms by which animals sense and respond to gravity. To identify the pathways involved in gravitational responses, we are isolating mutants of Drosophila melanogaster that show aberrant gravitaxic behavior. Our work has identified genes with roles in molecular signaling pathways and in neuronal circuitry that are involved in gravitaxic responses.
Publications
Ghosh, S., Bachilo, S. M., Simonette, R.A., Beckingham. K. M., Weisman, R. B. "Oxygen doping modifies near-infrared band gaps in fluorescent single-walled carbon nanotubes ." Science, 330: 1656-1659, 2010. (Chosen for mention in “This week in Science”, p.1583, with a figure from the paper displayed)
Bjorum, S.M., Simonette, R.A., Alanis, R., Wang, J.E., Lewis, B.M., Trejo, M.H., Hanson, K.A., Beckingham, K.M. The Drosophila BTB domain protein Jim Lovell has roles in multiple larval and adult behaviors. PLOS ONE
Kracklauer, M.P., Wiora, H.M., Chen, X., Deery, W.J., Bolival, B. Jr., Romanowicz, D., Simonette, R.A., Fuller, M.T., Fischer, J.A., and Beckingham, K.M. "The Drosophila SUN protein Dspag4 cooperates with the coiled-coil protein Yuri Gagarin to position the basal body on the spermatid nucleus." J Cell Science, 123: 2763-2772, 2010. (Chosen to provide the cover photo and for special mention in “In This Issue”, journal editorial comment page, J Cell Sci 123, e1603).
Texada, M.J., Deery, W. J., Simonette, R. A. and K.M. Beckingham “ Tropomyosin is a direct interaction partner of the Drosophila coiled coil protein Yuri Gagarin.” Experimental Cell Research, 317, 474-487, 2011.
Joshi, M.K., Moran, S.T., Beckingham, K.M. and K.R.MacKenzie The structure of androcam supports specialized interactions with myosin VI. Proceedings of the National Academy of Sciences, USA, 109 2012 Aug 14: 13290-13295
Beckingham, K.M. Synergy between stresses: an interaction between spaceflight-associated conditions and the microgravity response. Molecular Ecology, 19 2010: 4105-4107
Texada, M.J., and Beckingham, K.M. Tropomyosin is a direct interaction partner of Drosophila coiled coil protein yuri gagarin. Molecular Biology of the Cell 2008In Revision
Texada, M.J., Simonette, R.A., Johnson, C.B., Deery, W.J., and Beckingham, K.M. Yuri gagarin is required for actin, tubulin and basal body functions in Drosophila spermatogenesis. J. Cell. Sci., 121 2008: 1926-1936
Baker, D.A., Beckingham, K.M., and Armstrong, J.D. Functional dissection of the neural substrates for gravitaxic maze behavior. Journal of Comparative Neurology, 501 2007: 756-764
Leeuw, T.K., Reith, R.M., Simonette, R.A., Harden, M., Cherukuri, P., Tsyboulski, D., Beckingham, K.M., and Weisman, R.B. Single-walled nanotubes in the intact organism: Detection and biocompatibility studies in Drosophila. Nanoletters, 7 2007: 2650-2654
Pavlik, P., Konduri, V., Massa, E., Simonette, R., and Beckingham, K.M. A dicistronic gene pair within a cluster of "EF hand" protein genes in the genomes of Drosophila species. Genomics, 88 2006: 347-359
Frank, D.J., Martin, S.R., Gruender, B.N.T., Lee, Y-SR., Simonette, R. A., Bayley, P.M., Miller, K.G., and Beckingham, K.M. Androcam is a tissue-specific light chain for myosin VI in the Drosophila testis. Journal of Biological Chemistry, 281 2006: 24728-24736
Armstrong, J. D., Texada, M. J., Munjaal, R.V., Baker, D.A., and Beckingham, K. Gravitaxis in Drosophila: A forward genetic screen. Genes, Brain and Behavior, 5 2006: 222-239
Beckingham, K.M., Armstrong, J.D., Texada, M.J., Munjaal, R., and Baker, D. Drosophila melanogaster: The model organism of choice for the complex biology of multi-cellular rganisms. Gravitational and Space Biology, 18 2005: 1-13
Beckingham, K.M., Texada, M.J, Baker, D.A., Munjaal, R. and Armstrong, J.D. Graviperception in animals. Advances in Genetics, 55 2005: 106-145
Douglas, J.D., Texada, M.J., Munjaal, R., Baker, D., and Beckingham, K.M. Drosophila melanogaster: the model organism of choice for complex biology in complex organisms. Gravitational and Space Biology Bulletin 2004In Press
Beckingham, K.M. A proper sense of gravity: graviperception in insects. Grav. Space Biol. Bull., 18 2004: 3
Wang, B., Martin, S.R., Newman, R.A., Hamilton, S.L., Shea, M. A., Bayley, P. M., and Beckingham, K. Biochemical properties of V91G Calmodulin: a mutant calmodulin that deregulates muscle contraction in Drosophila. Protein Science, 13 2004: 3285-3297
Beckingham, K.M., Texada, M.J, Baker, D.A., Munjaal, R., and Armstrong, J.D. Genetics of graviperception in animals. Advances in Genetics, Elsevier Holland 2004In Revision
Andruss, B.F., Bolduc, C., and Beckingham, K. Transfer of calmodulin between cells of different tissue types in an intact organism. Genesis, 38 2004: 93-103
Wang, B., Sullivan, K. M. C. and Beckingham, K. Drosophila calmodulin mutations with specific defects in the musculature or nervous system. Genetics, 165 2003: 1340-1356
Munjaal, R.P., Texada, M.J., Armstrong, J.D., and Beckingham, K. Studies of Drosophila mutants with altered gravitaxic behavior. Gravitational and Space Biology Bulletin, 17 2003: 60
Wang, B., Bolduc, C., and Beckingham, K. Calmodulin UAS-constructs and the in vivo roles of calmodulin: Analysis of a muscle-specific phenotype. Genesis, 34 2002: 86-90
Shen, Y., Lee, Y-S., Soelaiman, S., Bergson, P., Lu, D., Chen, A., Beckingham, K., Grabarek, Z., Mrksich, M. and Tang, W-J. Physiological calcium concentrations regulate calmodulin binding and catalytic activity of adenylyl cyclase exotoxins. EMBO J., 21 2002: 6721-6732
Hetrick, G., Miller, C. S. and Beckingham, K. Role of the antennae in gravity sensing by Drosophila melanogaster. Gravitational and Space Biology Bulletin, 16 2002: 20
Kimbrell, D. A., Hice, C., Bolduc, C., Kleinhesselink, K. and Beckingham, K. The Dorothy enhancer has Tinman binding sites and drives hopscotch-induced tumor formation. Genesis, 24 2002: 23-28
Lee, S-J, Beckingham, K. and Stull, J.T. Calcium Independent Activity of Nitric oxide Synthase. Biochem. Biophys. Res. Comm., 284 2001: 526-530
Beckingham, K. Dwarfism. in Encyclopedia of Genetics, Eds. S. Brenner and J.H. Miller, Academic Press 2001
Beckingham, K. Genetic Diseases. in Encyclopedia of Genetics, Eds. S. Brenner and J.H. Miller, Academic Press 2001
Beckingham, K. Hunter's Syndrome. in Encyclopedia of Genetics, Eds. S. Brenner and J.H. Miller, Academic Press 2001
Rodney, G.G., Krol, J., Williams, B., Beckingham, K. and Hamilton, S.L. The Carboxy-terminal Calcium Binding Sites of Calmodulin Control Calmoldulin's Switch from an Activator to an Inhibitor of RYR1. Biochemistry, 40 2001: 12430-12435
Guptaroy, B., Marwaha, N., Pla, M., Wang, Z., Nelson, H. B., Beckingham, K. and Griffith, L. C. Alternative Splicing of Drosophila Calcium/Calmodulin-dependent Protein Kinase II Regulates Substrate Specificity and Activation. Mol. Brain Res., 80 2000: 26-34
Drum, C. L., Yan, S-Z., Sarac, R., Mabuchi, Y., Beckingham, K., Bohm, A., Grabarek, Z., and Tang, W-J. An Extended Conformation of Calmodulin Induces Interactions Between the Structural Domains of Adenylyl Cyclase from Bacillus anthracis to Promote Catalysis. J. Biol. Chem., 275 2000: 36334-36340
Lu, A.Q., and Beckingham, K. Androcam, a Drosophila Calmodulin-related Protein, Is Expressed Specifically in the Testes and Decorates Loop Kl-3 of the Y Chromosome. Mech. Development, 94 2000: 171-181
Markesich, D.C., Gajewski, K.M., Nazimiec, M.E. and Beckingham, K. Bicaudal Encodes the Drosophila beta NAC Homolog, a Component of the Ribosomal Translational Machinery. Development, 127 2000: 559-572
Armstrong, J.D., Texada, M.J., Carter, E.L., Kuo, E.S., Nadorff, C.M. and Beckingham, K. Gravitaxic Behavior in Drosophila melanogaster. Gravitational and Space Biology Bulletin, 14 2000: 23
Lee, S-J, Beckingham, K., and Stull, J.T. Mutations at Lysine 525 of Inducible Nitric Oxide Synthase Affect its Ca2+ Independent Activity. J. Biol.Chem., 275 2000: 36067-36072
Rodney, G.G, Williams, B.Y., Strasburg, G.M., Beckingham, K. and Hamilton, S.L. Regulation of RYR1 Activity by Ca2+ and Calmodulin. Biochemistry, 39 2000: 7807-7812
Bohni, R., Riesgo-Escovar, J., Oldham, S., Brogiolo, W., Stocker, H., Andruss, B.F., Beckingham, K., and Hafen, E. Autonomous Control of Cell and Organ Size by CHICO, a Drosophila Homolog of Vertebrate IRS1-4. Cell, 97 1999: 865-875
Fanger, C.M., Ghanshani, S., Logsdon, N.J., Rauer, H., Kalman, K., Zhou, J., Beckingham, K., Chandy, K.G., Cahalan, M.D. and Aiyar, J. Calmodulin Mediates Calcium-dependent Activation of the Intermediate Conductance KCa Channel, IKCa1. J. Biol. Chem., 274 1999: 5746-5754
Martin, S.R., Lu, A.Q., Xiao, J., Beckingham, K. and Bayley, P.M. Conformational and Metal-binding Properties of Androcam, a Testis-specific, Calmodulin-related Protein from Drosophila. Protein Science, 8 1999: 2444-2454
Stitzinger, S.M., Pellicena-Palle, A., Albrecht, E.B., Gajewski, K.M., Beckingham, K.M., and Salz, H.K. Mutations in the Predicted Aspartyl tRNA Synthetase of Drosophila Are Lethal and Function as Dosage-sensitive Maternal Modifiers of the Sex Determination Gene Sex-lethal. Mol. Gen. Genet., 261 1999: 142-151
Beckingham, K., Lu, A.Q., and Andruss, B.F. Calcium Binding Proteins and Development. Biometals, 11 1998: 359-373
Krueger, J.K., Bishop, N.A., Blumenthal, D.K., Zhi, G., Beckingham, K., Stull, J.T., and Trewhella, J. Calmodulin Binding to Myosin Light Chain Kinase Begins at Substoichiometric Ca2+ Concentrations: A Small-angle Scattering Study of Binding and Conformational Transitions. Biochemistry, 37 1998: 17810-17817
Zhu, T., Beckingham, K., and Ikebe, M. High Affinity Ca2+ Binding Sites of Calmodulin Are Critical for the Regulation of Myosin 1b Motor Function. J. Biol. Chem., 273 1998: 20481-20486
Beckingham, K., Bolduc, C. and Miettinen, S. Identification of Gravitaxis Mutant in Drosophila. Gravitational and Space Biology Bulletin, 12 1998: 66
Arredondo, L., Nelson, H.B., Beckingham, K., and Stern, M. Increased Transmitter Release and Aberrant Synaptic Morphology in a Drosophila Calmodulin Mutant. Genetics, 150 1998: 265-274
Magidin, M., and Beckingham, K. Use of GFP-Based Calcium and Calcium/calmodulin Sensors to Investigate Mechanical Stimulation. Gravitational and Space Biology Bulletin, 12 1998: 13