Jon Audhya

Research Interests

Our laboratory is committed to understanding fundamental mechanisms by which membrane proteins, lipids, and other macromolecules are transported throughout eukaryotic cells. To do so, we take advantage of numerous interdisciplinary approaches, including biochemistry, structural biology, biophysics, genetics, molecular biology and high resolution fluorescence and electron microscopy.

Additionally, we use a variety of experimental systems, ranging from simple animal models (e.g. Caenorhabditis elegans) to human induced pluripotent stem cells (iPSCs). We also aim to recapitulate individual steps of membrane transport in vitro, using recombinant proteins and chemically defined lipids. Our ultimate goal is to identify the regulatory pathways that control membrane deformation, which enable vesicle formation in the endosomal and secretory systems. Although basic research is the cornerstone of our program, we also seek to define pathomechanisms that underlie human disease, focusing on the impact of mutations in key trafficking components that lead to cancer, neurodegeneration, asthma, and diabetes. For more information, please visit our lab webpage: www.audhyalab.org .

• Slosarek, E.L.^#, Schuh, A.L.^#, Pustova, I.^#, Johnson, A., Bird, J., Johnson, M., Frankel, E.B., Bhattacharya, N., Hanna, M.G., Burke, J.E., Ruhl, D.A., Quinney, K., Block, S., Peotter, J.L., Chapman, E.R., Sheets, M.D., Butcher, S.E., Stagg, S.M., and Audhya, A. (2018) Pathogenic TFG mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and axon fasciculation. Cell Rep. In press. (^# denotes equal contribution)

• Frankel, E.B., Shankar, R., Moresco, J.J., Yates, J.R., Volkmann, N., and Audhya, A. (2017) Ist1 regulates ESCRT-III assembly and function during multivesicular endosome biogenesis in Caenorhabditis elegans embryos. Nat. Commun. 8:  1439.

• Hanna, M.G., Block, S., Frankel, E.B., Hou, F., Johnson, A., Yuan, L., Knight, G., Moresco, J.J., Yates, J.R., Ashton, R., Schekman, R., Tong, Y., and Audhya, A. (2017) TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER-Golgi intermediate compartments. Proc. Natl. Acad. Sci. USA. 114:  E7707-E7716.

•Konig, J., Frankel, E.B., Audhya, A.*, and Muller-Reichert, T.* (2017) Membrane remodeling during embryonic abscission in Caenorhabditis elegans. J. Cell Biol. 216: 1277-1286. (* denotes co-corresponding authors)

• Wang, L., Johnson, A., Hanna, M., and Audhya, A. (2016) Eps15 membrane binding and bending activity acts redundantly with Fcho1 during clathrin-mediated endocytosis. Mol. Biol. Cell. 27:  2676-2687. (Cover)

• Hanna, M.G., Mela, I., Wang, L., Henderson, R.M., Chapman, E.R., Edwardson, J.M., and Audhya, A. (2016) Sar1 GTPase activity is regulated by membrane curvature. J. Biol. Chem. 291: 1014-1027.

• Johnson, A., Bhattacharya, N., Hanna, M., Pennington, J.G., Schuh, A.L., Wang, L., Otegui, M.S., Stagg, S.M., and Audhya, A. (2015) TFG clusters COPII-coated transport carriers and promotes early secretory pathway organization. EMBO J. 34:  811-827.

• Shen, Q., Schuh, A.L. Zheng, Y., Quinney, K., Wang, L., Hanna, M., Mitchell, J.C., Otegui, M.S., Ahlquist, P., Cui, Q., and Audhya, A. (2014) Mechanisms governing ESCRT-III spiral filament assembly. J. Cell Biol. 206:  763-777. (Cover)

• Mayers, J.R., Wang, L., Pramanik, J., Johnson, A., Sarkeshik, A., Wang, Y., Saengsawang, W., Yates, J.R., and Audhya, A. (2013) Regulation of ubiquitin-dependent cargo sorting by multiple plasma membrane endocytic adaptor proteins. Proc. Natl. Acad. Sci. USA. 110:  11857-11862.

• Beetz, C., Johnson, A., Schuh, A., Thakur, S., Varga, R., Fothergill, T., Hertel, N., Bomba-Warczak, E., Thiele, H., Nurnberg, G., Altmuller, J., Saxena, R., Chapman, E.R., Dent, E.W., Nurnberg, P., and Audhya, A. (2013) Inhibition of TFG function causes hereditary axon degeneration by impairing ER structure. Proc. Natl. Acad. Sci. USA. 110:  5091-5096.

• Morrison, K., Witte, K., Mayers, J.R., Schuh, A.L., and Audhya, A. (2012) Role of acidic phospholipids and nucleotides in regulating membrane binding and activity of a calcium-independent phospholipase A2 isoform. J. Biol. Chem. 287:  38824-38834.

• Fyfe, I.^#, Schuh, A.L.^#, Edwardson, J.M., and Audhya, A. (2011) Association of the endosomal sorting complex ESCRT-II with the Vps20 subunit of ESCRT-III generates a curvature sensitive protein complex capable of nucleating filaments of ESCRT-III. J. Biol. Chem. 286:  34262-34270. (^# denotes equal contribution)

• Witte, K., Schuh, A.L., Hegermann, J., Sarkeshik, A., Mayers, J.R., Schwarze, K., Yates, J.R., Eimer, S., and Audhya, A. (2011) TFG-1 function in protein secretion and oncogenesis. Nat. Cell Biol. 13:  550-558.