My laboratory is interested in the regulatory interfaces between novel lipid-mediated signal transduction pathways and important cellular functions. The focus of our work is the phosphatidylinositol/ phosphatidylcholine transfer proteins (PITPs), a ubiquitous but enigmatic class of proteins. Ongoing projects in the laboratory derive from a multidisciplinary approach that encompasses biochemical characterization of novel members of the metazoan PITP family, and the application of genetic, molecular and biophysical approaches to detailed structural and functional analyses of PITPs. The laboratory breaks down into two groups: a group that studies the mechanism of function of yeast PITPs, and a group that generates knockout mice and analyzes the function of specific PITP isoforms in the mammal. Our collective evidence indicates that PITPs coordinate key interfaces of lipid-driven metabolic reactions and intracellular signaling pathways in both yeast and mammals. Inappropriate regulation of these interfaces compromises membrane trafficking events, growth factor receptor function, cell growth control, and regulation of key developmental pathways. Because defects in any one of these pathways define recognized mechanisms cancer-potentiating mechanisms, PITPs represent essentially unstudied regulators whose dysfunction is likely to influence the activities of cellular processes required for cellular homeostasis. Of additional interest is our recent finding that one of our PITP-deficient mouse lines potentially provides a unique model for chylomicron retention disease, hypoglycemia and brain inflammatory disease. Relevant approaches that the laboratory employs include: molecular biology, protein and lipid biochemistry, confocal and electron microscopy, mouse gene knockout technology, and classical and molecular genetics.

Schaaf, G., Ortlund, E.A., Tyeryar, K.R., Mousley, C.J., Ile, K.E., Garrett, T.A., Ren, J., Woolls, M.J., Raetz, C.R.H., Redinbo, M.R., and Bankaitis, V.A. 2008. Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily. Mol. Cell 29: 191- 206.

Ryan, M.M., Temple, B.R.S., Phillips, S.E., and Bankaitis, V.A. 2007. Conformational dynamics of the major yeast phosphatidylinositol transfer protein Sec14p: Insights into the mechanisms of phospholipid exchange and diseases of Sec14p-like protein deficiencies. Mol. Biol. Cell 18: 1928-1942.

Smirnova, T., Chadwick, T.G., MacArthur, R., Poluekov, O., Song, L., Ryan, M., Schaaf, G., and Bankaitis, V.A. 2006. The chemistry of phospholipid binding by the Saccharomyces cerevisiae phosphatidylinositol transfer protein Sec14p as determined by electron paramagnetic resonance spectroscopy. J. Biol. Chem. 281: 34897-34908.

Ile, K.E., Schaaf, G., and Bankaitis, V.A. 2006. Phosphatidylinositol transfer proteins and cellular nanoreactors for lipid signaling. Nature Chem. Biol. 2: 576-583.

Slessareva, J.E., Routt. S.M., Temple, B., Bankaitis, V.A., and Dohlman, H.G. 2006. G protein activation of a PtdIns 3-kinase at the endosome. Cell 126: 191-203.

Phillips, S.E., Ile, K., Boukhelifa, M., Huijbregts R.P.H., and Bankaitis, V.A. 2006. Specific and nonspecific membrane binding determinants cooperate in targeting phosphatidylinositol transfer protein b-isoform to the murine trans-Golgi network. Mol. Biol. Cell 17: 2498-2512.

Vincent, P., Chua, M., Nogue, F., Fairbrother, A., Mekheel, H., Xu, Y., Allen, N., Bibikova, T.N., Gilroy, S., and Bankaitis, V.A. 2005. A Sec14p-nodulin domain phosphatidylinositol transfer protein polarizes membrane growth of Arabidopsis root hairs. Journal of Cell Biology 168: 801-812.

Alb, J.G. Jr., Cortese, J.D., Phillips, S.E., Albin, R.L., Nagy, T.R., Hamilton, B.A., and Bankaitis, V.A. 2003. Mice lacking phosphatidylinositol transfer protein alpha exhibit spinocerebellar degeneration, intestinal and hepatic steatosis, and hypoglycemia. J. Biol. Chem. 278: 33501-33518.

Li, X., Rivas, M.P., Fang, M., Marchena, J., Mehrotra, B., Chaudhary, A., Feng, L., Prestwich, G.D., and Bankaitis, V.A. 2002. Analysis of oxysterol binding protein homolog Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex. Journal of Cell Biology 157: 63-77.

Bankaitis, V.A. 2002. The mammalian trans-Golgi network reveals a slick new recruiting tool. Science 295: 325-328.

Sha, B., Phillips, S.E., Bankaitis, V.A. and Luo, M. 1998. Crystal structure of the Saccharomyces cerevisiae phosphatidylinositol transfer protein Sec14p. Nature 391: 506-510.

Kearns, B.G., McGee T.P., Mayinger, P., Gedvilaite, A., Phillips, S.E., Kagiwada, S., and Bankaitis, V.A. 1997. Essential role for diacylglycerol in protein transport from the yeast Golgi complex. Nature 387: 101-105.

Ohashi, M., de Vries, K.J., Frank, R., Snoek, G., Bankaitis, V., Wirtz, K., and Huttner, W.B. 1995. A role for phosphatidylinositol transfer protein in secretory vesicle formation. Nature 377: 544-547.

Brennwald, P., B.G. Kearns, K.M. Champion, S. Keränen, V.A. Bankaitis, and Novick, P.J. 1994. Sec9 is a SNAP-25-like component of a yeast SNARE complex that may be the effector of Sec4 function in exocytosis. Cell 79: 245-258.

Cleves, A. E., T. P. McGee, E. A. Whitters, K. Champion, J. R. Aitken, W. Dowhan, M. Goebl, and V. A. Bankaitis. 1991. Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass the requirement for an essential phospholipid transfer protein. Cell 64: 789-800.

Bankaitis, V. A., J. F. Aitken, A. E. Cleves, and W. Dowhan. 1990. An essential role for a phospholipid transfer protein in yeast Golgi function. Nature 347: 561-562.

Collier, D. N., V. A. Bankaitis, J. B. Weiss, and P. J. Bassford, Jr. 1988. The anti-folding activity of SecB promotes the export of the Escherichia coli maltose-binding protein. Cell 53: 273-283.

Johnson, L. M., V. A. Bankaitis, and S. D. Emr. 1987. Distinct sequence determinants directing intracellular sorting and modification of a yeast vacuolar protease. Cell 48: 875-885.

Bankaitis, V. A., B. A. Rasmussen, and P. J. Bassford, Jr. 1984. Intragenic suppressor mutations that restore export of maltose binding protein with a truncated signal peptide. Cell 37: 243-252.