Biomembranes: Function and regulation of lipid pumps
Metabolic processes in eukaryotic cells are compartmentalized into distinct membrane-bound organelles that display striking differences in the composition, texture and sidedness of their membrane lipids. We are interested in understanding how cells establish and maintain these differences in lipid organization. In particular, we have focused our work on mechanisms of the protein-mediated translocation of lipids across cellular membranes and their intracellular transport to distinct organelles as well as the physiological relevance and function of the protein-mediated lipid transport. To this end, we have developed a variety of biophysical methods to study those transport processes and established various protocols to synthesize specific lipid probes. Within the frame of national and international co-operations we are currently working on the identification and characterization of lipid-transporting proteins (lipid flippases).
Marek M, Milles S, Schreiber G, Daleke DL, Dittmar G, Herrmann A, Müller P, Pomorski TG (2011) The yeast plasma membrane ATP binding cassette (ABC) transporter Aus1: purification, characterization, and the effect of lipids on its activity. J Biol Chem. 286, 21835-21843.
Weingärtner A, Drobot B, Herrmann A, Sánchez-Cañete MP, Gamarro F, Castanys S and Pomorski TG (2010) Disruption of the Lipid-Transporting LdMT-LdRos3 Complex in Leishmania donovani Affects Membrane Lipid Asymmetry but Not Host Cell Invasion. PLoS ONE 5(8): e12443. doi:10.1371/journal.pone.0012443
López-Marqués RL, Poulsen RL, Hanisch S, Meffert K, Buch-Pedersen MJ, Jakobsen MK, Pomorski TG and Palmgren MG (2009) Intracellular targeting signals and lipid specificity determinants of the ALA/ALIS P4-ATPase complex reside in the catalytic ALA α-subunit. Mol. Biol. Cell 21, 791-801.
Poulsen LR, López-Marqués RL, McDowell SC, Okkeri J, Licht D, Pomorski T, Harper JF and Palmgren MG (2008). A Golgi localized Arabidopsis thaliana P4-ATPase involved in root and shoot development requires a β subunit to gain functionality. Plant Cell 20, 658-676.
Papadopulos A, Vehring S, Lopez-Montero I, Kutschenko L, Stockl M, Devaux PF, Kozlov M, Pomorski T, Herrmann A (2007). Flippase activity detected with unlabelled lipids by shape changes of giant unilamellar vesicles. J. Biol. Chem. 282, 15559-15568.
Alder-Baerens N, Lisman Q, Luong L, Pomorski T and Holthuis JCM. (2006). Loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles. Mol. Biol. Cell 17, 1632-1642.
Pomorski T, Lombardi R, Riezman H, Devaux PF, van Meer G, Holthuis JCM (2003). Drs2p-related P-type ATPases Dnf1p and Dnf2p Are Required for Phospholipid Translocation across the Yeast Plasma Membrane and Serve a Role in Endocytosis. Mol. Biol. Cell 14, 1240-1254