Public Health Relevance

Defects in human P4-ATPases cause mental retardation and familial intrahepatic cholestasis. Studies with mice have further implicated P4-ATPases in immune deficiency, type 2 diabetes, hearing loss and hepatic cancer. Defining the mechanism of P4-ATPase function will further our understanding of these diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM107978-07
Application #
9853802
Study Section
Biochemistry and Biophysics of Membranes Study Section (BBM)
Program Officer
Nie, Zhongzhen
Project Start
2013-09-01
Project End
2022-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
965717143
City
Nashville
State
TN
Country
United States
Zip Code
37203
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Roland, Bartholomew P; Graham, Todd R (2016) Decoding P4-ATPase substrate interactions. Crit Rev Biochem Mol Biol 51:513-527
van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C et al. (2016) Exploring genetic suppression interactions on a global scale. Science 354:
Roland, Bartholomew P; Graham, Todd R (2016) Directed evolution of a sphingomyelin flippase reveals mechanism of substrate backbone discrimination by a P4-ATPase. Proc Natl Acad Sci U S A 113:E4460-6
Takar, Mehmet; Wu, Yuantai; Graham, Todd R (2016) The Essential Neo1 Protein from Budding Yeast Plays a Role in Establishing Aminophospholipid Asymmetry of the Plasma Membrane. J Biol Chem 291:15727-39
Hankins, Hannah M; Sere, Yves Y; Diab, Nicholas S et al. (2015) Phosphatidylserine translocation at the yeast trans-Golgi network regulates protein sorting into exocytic vesicles. Mol Biol Cell 26:4674-85
Hankins, Hannah M; Baldridge, Ryan D; Xu, Peng et al. (2015) Role of flippases, scramblases and transfer proteins in phosphatidylserine subcellular distribution. Traffic 16:35-47
Zhou, Xiaoming; Sebastian, Tessy T; Graham, Todd R (2013) Auto-inhibition of Drs2p, a yeast phospholipid flippase, by its carboxyl-terminal tail. J Biol Chem 288:31807-15
Xu, Peng; Baldridge, Ryan D; Chi, Richard J et al. (2013) Phosphatidylserine flipping enhances membrane curvature and negative charge required for vesicular transport. J Cell Biol 202:875-86
Baldridge, Ryan D; Xu, Peng; Graham, Todd R (2013) Type IV P-type ATPases distinguish mono- versus diacyl phosphatidylserine using a cytofacial exit gate in the membrane domain. J Biol Chem 288:19516-27

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