帕特里夏·凯恩博士

研究抽象

All eukaryotic cells tightly control cellular pH. Proper control of cytoplasmic pH is essential for normal metabolism and cell growth, and acidification of organelles such as the lysosome, 核内体, and Golgi apparatus is essential for 蛋白质排序 and degradation, 离子体内平衡, and signal transduction. The vacuolar ATPase (V-ATPase) is one of the central players in pH control. All eukaryotic cells have V-ATPases of remarkably similar structure, and loss of V-ATPase 函数 is lethal at early stages of development in higher eukaryotes and conditionally lethal in fungi.

The yeast V-ATPase has proven to be an excellent model for studies of V-ATPase structure, 函数, 和监管. Work in my laboratory addresses three major questions using yeast as a model system: 1) definition of 函数al and structural relationships among the fourteen subunits of the V-ATPase 2) regulation of the V-ATPase in vivo, 3) physiological implications of organelle acidification. We approach these questions using a combination of biochemical, 遗传, 分子, and cell biological methods. Our studies of subunit structure and 函数 combine traditional biochemistry and yeast 遗传s with insights from the growing number of complete eukaryotic genomes now available. Regulation of V-ATPases is proving to be rich and complex. Assembled V-ATPases can rapidly and reversibly dissociate in vivo in response to changes in growth conditions, and this appears to be a major regulatory mechanism. Current work is directed toward defining this signal transduction pathway and probing the possibility of crosstalk between V-ATPase regulation and other pathways and processes. 最后, V-ATPases are implicated in a number of unexpected roles, including resistance to oxidative stress. We seek to better understand these rolls and their links to overall cellular pH control.

选择参考:

Zhang Z, Zheng Y, Mazon H, Milgrom E, Kitagawa N, Kish-Trier E, Heck AJ, 凯恩点, Wilkens S. Structure of the yeast vacuolar ATPase. 生物化学. 2008 Dec 19;283(51):35983-95. Epub 2008年10月27日.

Chen S, Tarsio M, 凯恩点, Greenberg ML. Cardiolipin mediates cross-talk between mitochondria and the vacuole. Mol生物细胞. 2008 Dec;19(12):5047-58. Epub 2008年9月17日.

凯恩点. The long physiological reach of the yeast vacuolar H+-ATPase. J生物能源. 2007 Dec;39(5-6):415-21. 审查.

上午是Smardon，下午是Kane. RAVE is essential for the efficient assembly of the C subunit with the vacuolar H(+)-ATPase. 生物化学. 2007 Sep 7;282(36):26185-94. 2007年7月10日.

Rizzo JM, Tarsio M, Mart�nez-Mu�oz GA, 凯恩点. Diploids heterozygous for a vma13Delta mutation in Saccharomyces cerevisiae highlight the importance of V-ATPase subunit balance in supporting vacuolar acidification and silencing cytosolic V1-ATPase activity. 生物化学. 2007 Mar 16;282(11):8521-32. Epub 2007年1月18日.

Milgrom E, Diab H, Middleton F, 凯恩点. Loss of vacuolar proton-translocating ATPase activity in yeast results in chronic oxidative stress. 生物化学. 2007 Mar 9;282(10):7125-36. Epub 2007年1月10日.