Yuxin Mao
Associate Professor

Yuxin Mao

Phone

607-255-0783

Address

Department of Molecular Biology & Genetics
357 Weill Hall
Cornell University
Ithaca, NY 14853-2703

Email

Web Sites

Department Profile
Lab Website

Background

Yuxin Mao is an Associate Professor of Molecular Biology and Genetics and a member of the Weill Institute for Cell and Molecular Biology (Weill Institute). Dr. Yuxin Mao received a B.S. in Molecular Biology and Biochemistry from Nankai University in China and a Ph.D. in Structural Biology from Baylor College of Medicine. He did his postdoctoral research at Yale University School of Medicine, Department of Cell Biology where he was awarded a HHMI postdoctoral fellowship from the Life Sciences Research Foundation.

Research Description

Our laboratory is interested in understanding the mechanisms regulating membrane trafficking. Living cells are highly organized by intracellular membrane separated compartments. However, each compartment is not an isolated island, these lipid bilayer-bound organelles constitutively communicate with each other through signal and material flows by vesicular trafficking. Each vesicular trafficking reaction can be dissected in multiple steps, including vesicle budding from donor organelles, mobilization, docking, and fusion with targeting organelles. Each step is tightly regulated to ensure proper spatial and temporal delivery of vesicular cargoes. Two key regulatory mechanisms are the modification of inositol lipids through phosphorylation and dephosphorylation and the ubiquitination of cargo or transport machinery proteins.

Phosphorylation of the inositol ring of phosphoinositides generates seven unique stereoisomers that have been identified in vivo and have different subcellular localization. Each membrane compartment has its unique inositol lipids composition. During vesicular trafficking, phosphotidylinositols (PI) are phosphorylated or dephosphorylated by a variety of PI kinases and phosphatases, which appear to function at distinct intracellular compartments.

On the other hand, through the ubiquitination of cargo proteins or transporting machinery proteins, cells create a transient binding platform which is recognized by ubiquitin binding modules. Thus, ubiquitinated proteins and ubiquitin binding proteins form a protein-protein interaction network, which relays the transporting vesicle to its destination.

By using structural tools (both X-ray and NMR), as well as molecular, biochemical and cellular biological techniques, we aim to elucidate the structure and function of those macromolecules involved in inositol lipids recognition, interaction, and modification. Meanwhile, we are also interested in the structure and underlying mechanisms of endocytic proteins regulated by ubiquitination.

Publications

Stefan CJ, Manford AG, Baird D, Yamada-Hanff J, Mao Y, Emr SD. Osh Proteins Regulate Phosphoinositide Metabolism at ER-Plasma Membrane Contact Sites. Cell. 2011, 144(3):389-401.

Brady OA, Meng PS, Zheng Y, Mao Y and Hu F. Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1 Journal of Neurochemistry 2011, 116(2):248-59

Andrew Manford, Tian Xia, Ajay Kumar Saxena, Christopher Stefan, Fenghua Hu, Scott D. Emr, Yuxin Mao. Crystal Structure of the Yeast Sca1: Implication for its Phosphoinositide Phosphatase Function EMBO J. (2010) 29(9): p. 1489-98.

Yuxin Mao, Daniel M. Balkin, Robert Zoncu, Kai S. Erdmann, Livia Tomasini, Fenghua Hu, Moonsoo M. Jin, Michael E. Hodsdon and Pietro De Camilli. A PH domain within OCRL bridges clathrin mediated membrane trafficking to metabolism. EMBO J. (2009), 28(13): 1831-42.

Valeria Facchinetti, Weiming Ouyang, Hua Wei, Nelyn Soto, Adam Lazorchak, Christine Gould, Carolyn Lowry, Alexandra C. Newton, Yuxin Mao, Robert . Maio, William C. Sessa, Jun Qin, Pumin Zhang, Bing Su and Estela Jacinto. The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J. (2008), 27, 1932-1943.

Kai S. Erdmann*, Yuxin Mao*, Heather J. McCrea*, Roberto Zoncu, Sangyoon Lee, Summer Paradise, Jan Modregger, Daniel Biemesderfer, Derek Toomre and Pietro De Camilli. A role of the Lowe Syndrome protein OCRL in early steps of the endocytic pathway. Dev Cell. (2007), 13 (3):377-90. (*equal contribution)

Valeria Facchinetti, Weiming Ouyang, Chang-chih Wu, Nelyn Soto, Carolyn Lowry, Adam Lazorchak, Christine Gould, Alexandra C. Newton, Kun-Liang Guan, Yuxin Mao, Robert Q. Miao, William C. Sessa, Jun Qin, Bing Su, and Estela Jacinto. Phosphorylation of the turn motif by mTORC2 during translation protects Akt and PKC from proteasome degradation. (in press).

Yuxin Mao, Francesca Senic-Matuglia, Pier Paolo Di Fiore, Simona Polo, Michael E. Hodsdon and Pietro De Camilli. De-ubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain, PNAS. (2005) 102(36):12700-5.

Yuxin Mao*, Nand K. Vyas*, Meenakshi N. Vyas, Dong-Hua Chen, Steve J. Ludtke, Wah Chiu and Florante A. Quiocho. Structure of the bifunctional and Golgi-associated formiminotransferase cyclodeaminase octamer, EMBO J. (2004) 23: 2963-2971. (*equal contribution)

Takashima H, Boerkoel CF, John J, Saifi GM, Salih MA, Armstrong D, Mao Y, Quiocho FA, Roa BB, Nakagawa M, Stockton DW, Lupski JR. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy, Nat. Genet., (2002) 32(2):267-72.

Olli Lohi, Anssi Poussu, Yuxin Mao, Florante Quiocho and Veli-Pekka Lehto (2002) VHS domain - a longshoreman of vesicle lines, FEBS Letters (513) 19-23.

Yuxin Mao, Jue Chen, Bing Zhang, Jennifer A. Maynard and Florante A. Quiocho (2001). A Novel All Helix Fold of the AP180 Amino-Terminal Domain for Phosphoinositide Binding and Clathrin Assembly in Synaptic Vesicle Endocytosis, Cell, (104) 433-440.

Yuxin Mao, Alexei Nickitenko, Xiaoqun Duan, Thomas E. Lloyd, Mark N. Wu, Hugo Bellen, and Florante A. Quiocho. (2000). Crystal Structure of the VHS and FYVE Tandem Domains of Hrs, a Protein Involved in Membrane Trafficking and Signal Transduction, Cell, (100) 447-456.

Jun Ye, Yuxin Mao, Lulu Gui, Wenrui Chang and Dongcai Liang, (2000), Crystal Structure Studies of Destripeptide (B28-B30) Insulin, Sciences in China, Ser. B, 43 (2) 178-186.

Yuxin Mao, Mei Li, Zhuli Wan, Tao Jiang, Xiaoming An, Dongcai Liang, Fang Liu, Chunmei Huang, Laitong Chen, Meihao Hu. (1999). Preparation of Destripeptide (B28-B30) Insulin and Destetrapeptide (B27-B30) Insulin and Preliminary X-ray Crystallographic Study of Destripeptide insulin, Progress in Natural Sciences, 9(3) 241-247.