Ca 2+ is known to have several important intracellular regulatory roles in all eucaryotes. Some of the cellular processes and functions controlled by Ca 2+ include cellular differentiation, cell movement, endocytosis, morphogenesis, mitosis, secretion, cell division, mating, cell and nuclear fusion. However, the precise function of Ca 2+ in most of these processes has not been established, and the situation is further complicated because all these Ca 2+ mediated processes occur in conjunction with one another. The model eucaryote, S. cerevisiae is probably the best experimental system in which to dissect these elusive but ubiquitous cellular responses to Ca 2+. However, to understand completely the role of Ca 2+ as a secondary messenger we must first elucidate the mechanisms responsible for regulating cytosolic Ca 2+ levels. This will require an understanding of the mechanism, and regulation of Ca 2+ movement across the plasma membrane and Ca 2+ uptake and release by the various yeast organelles. The specific goal of the research project is to isolate and characterize mutants defective in regulation of cytosolic Ca 2+ levels, and to use these mutants to identify genes (and their encoded proteins) which are responsible for maintaining normal cytosolic Ca 2+ levels.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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Henry M. Jackson Fdn for the Adv Mil/Med
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Dunn, T M; Haak, D; Monaghan, E et al. (1998) Synthesis of monohydroxylated inositolphosphorylceramide (IPC-C) in Saccharomyces cerevisiae requires Scs7p, a protein with both a cytochrome b5-like domain and a hydroxylase/desaturase domain. Yeast 14:311-21
Garnepudi, V R; Zhao, C; Beeler, T et al. (1997) Serine palmitoyltransferase (scs1/lcb2) mutants have elevated copy number of the L-A dsRNA virus. Yeast 13:299-304
Beeler, T J; Fu, D; Rivera, J et al. (1997) SUR1 (CSG1/BCL21), a gene necessary for growth of Saccharomyces cerevisiae in the presence of high Ca2+ concentrations at 37 degrees C, is required for mannosylation of inositolphosphorylceramide. Mol Gen Genet 255:570-9
Beeler, T; Gable, K; Dunn, T (1997) Activation of divalent cation influx into S. cerevisiae cells by hypotonic downshift. J Membr Biol 160:77-83
Beeler, T; Bruce, K; Dunn, T (1997) Regulation of cellular Mg2+ by Saccharomyces cerevisiae. Biochim Biophys Acta 1323:310-8
Fu, D; Beeler, T J; Dunn, T M (1995) Sequence, mapping and disruption of CCC2, a gene that cross-complements the Ca(2+)-sensitive phenotype of csg1 mutants and encodes a P-type ATPase belonging to the Cu(2+)-ATPase subfamily. Yeast 11:283-92
Fu, D; Beeler, T; Dunn, T (1994) Sequence, mapping and disruption of CCC1, a gene that cross-complements the Ca(2+)-sensitive phenotype of csg1 mutants. Yeast 10:515-21
Zhao, C; Beeler, T; Dunn, T (1994) Suppressors of the Ca(2+)-sensitive yeast mutant (csg2) identify genes involved in sphingolipid biosynthesis. Cloning and characterization of SCS1, a gene required for serine palmitoyltransferase activity. J Biol Chem 269:21480-8
Beeler, T J; Gable, K S (1994) Phosphate, nitrendipine and valinomycin increase the Ca2+/ATP coupling ratio of rat skeletal muscle sarcoplasmic reticulum Ca(2+)-ATPase. Biochim Biophys Acta 1189:189-94
Dunn, T; Gable, K; Beeler, T (1994) Regulation of cellular Ca2+ by yeast vacuoles. J Biol Chem 269:7273-8

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