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Thomas Günther Pomorski

Bio: Thomas Günther Pomorski is an academic researcher from Ruhr University Bochum. The author has contributed to research in topics: Flippase & Phospholipid. The author has an hindex of 39, co-authored 106 publications receiving 4446 citations. Previous affiliations of Thomas Günther Pomorski include Humboldt University of Berlin & Humboldt State University.


Papers
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Journal ArticleDOI
TL;DR: It appears that Dnf1p, DnF2p and Drs2p each help regulate the transbilayer lipid arrangement in the plasma membrane, and that this regulation is critical for budding endocytic vesicles.
Abstract: Plasma membranes in eukaryotic cells display asymmetric lipid distributions with aminophospholipids concentrated in the inner and sphingolipids in the outer leaflet This asymmetry is maintained by

360 citations

Journal ArticleDOI
TL;DR: This review ascribes the sorting power of the Golgi to its capability to act as a distillation apparatus for sphingolipids and cholesterol, and hypothesize that by this mechanism, the composition of the sphingoipid domains, and the surrounding membrane changes along the cis-trans axis.
Abstract: Eukaryotes are characterized by endomembranes that are connected by vesicular transport along secretory and endocytic pathways. The compositional differences between the various cellular membranes ...

317 citations

Journal ArticleDOI
TL;DR: This review summarizes recent progress on the identification and characterization of the various flippases and the demonstration of their biological functions.
Abstract: The typically distinct phospholipid composition of the two leaflets of a membrane bilayer is generated and maintained by bi-directional transport (flip-flop) of lipids between the leaflets. Specific membrane proteins, termed lipid flippases, play an essential role in this transport process. Energy-independent flippases allow common phospholipids to equilibrate rapidly between the two monolayers and also play a role in the biosynthesis of a variety of glycoconjugates such as glycosphingolipids, N-glycoproteins, and glycosylphosphatidylinositol (GPI)-anchored proteins. ATP-dependent flippases, including members of a conserved subfamily of P-type ATPases and ATP-binding cassette transporters, mediate the net transfer of specific phospholipids to one leaflet of a membrane and are involved in the creation and maintenance of transbilayer lipid asymmetry of membranes such as the plasma membrane of eukaryotes. Energy-dependent flippases also play a role in the biosynthesis of glycoconjugates such as bacterial lipopolysaccharide. This review summarizes recent progress on the identification and characterization of the various flippases and the demonstration of their biological functions.

290 citations

Journal ArticleDOI
TL;DR: Recent studies in yeast, parasites such as Leishmania, and mammalian cells have identified several candidates for lipid flippases, and whereas some of these serve a fundamental role in the release of lipids from cells, others appear to have unexpected and important functions in vesicular traffic.
Abstract: The various organellar membranes of eukaryotic cells display striking differences in the composition, leaflet distribution and transbilayer movement of their lipids. In membranes such as the endoplasmic reticulum, phospholipids can move readily across the bilayer, aided by membrane proteins that facilitate a passive equilibration of lipids between both membrane halves. In the plasma membrane, and probably also in the late Golgi and endosomal compartments, flip-flop of phospholipids is constrained and subject to a dynamic, ATP-dependent regulation that involves members of distinct protein families. Recent studies in yeast, parasites such as Leishmania, and mammalian cells have identified several candidates for lipid flippases, and whereas some of these serve a fundamental role in the release of lipids from cells, others appear to have unexpected and important functions in vesicular traffic: their activities are required to support vesicle formation in the secretory and endocytic pathways.

197 citations

Journal ArticleDOI
15 Dec 2006-Blood
TL;DR: It is demonstrated for the first time that externalized PS on Ag-stimulated CTLs is linked to T-cell activation and probably involved in cell-to-cell contact formation at the immunologic synapse.

157 citations


Cited by
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Journal ArticleDOI
TL;DR: How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functions of their individual membranes?
Abstract: Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?

5,720 citations

Journal ArticleDOI
TL;DR: The ATP-binding cassette (ABC) transporters are essential for many processes in the cell and mutations in these genes cause or contribute to several human genetic disorders including cystic fibrosis, neurological disease, retinal degeneration, cholesterol and bile transport defects, anemia, and drug response.

2,159 citations

Journal ArticleDOI
TL;DR: The lifetime of a photophysical process is the time required by a population of N electronically excited molecules to be reduced by a factor of e via the loss of energy through fluorescence and other non-radiative processes and the average length of time τ is called the mean lifetime, or simply lifetime.
Abstract: When a molecule absorbs a photon of appropriate energy, a chain of photophysical events ensues, such as internal conversion or vibrational relaxation (loss of energy in the absence of light emission), fluorescence, intersystem crossing (from singlet state to a triplet state) and phosphorescence, as shown in the Jablonski diagram for organic molecules (Fig. 1). Each of the processes occurs with a certain probability, characterized by decay rate constants (k). It can be shown that the average length of time τ for the set of molecules to decay from one state to another is reciprocally proportional to the rate of decay: τ = 1/k. This average length of time is called the mean lifetime, or simply lifetime. It can also be shown that the lifetime of a photophysical process is the time required by a population of N electronically excited molecules to be reduced by a factor of e. Correspondingly, the fluorescence lifetime is the time required by a population of excited fluorophores to decrease exponentially to N/e via the loss of energy through fluorescence and other non-radiative processes. The lifetime of photophycal processes vary significantly from tens of femotoseconds for internal conversion1,2 to nanoseconds for fluorescence and microseconds or seconds for phosphorescence.1 Open in a separate window Figure 1 Jablonski diagram and a timescale of photophysical processes for organic molecules.

1,829 citations

Journal ArticleDOI
TL;DR: Understanding the host–microbial interactions that lead to neoplasia will improve cancer-targeted therapeutics and diagnostics, and provide mechanistic insights into other malignancies that arise within the context of microbially initiated inflammatory states.
Abstract: Although gastric adenocarcinoma is associated with the presence of Helicobacter pylori in the stomach, only a small fraction of colonized individuals develop this common malignancy. H. pylori strain and host genotypes probably influence the risk of carcinogenesis by differentially affecting host inflammatory responses and epithelial-cell physiology. Understanding the host-microbial interactions that lead to neoplasia will improve cancer-targeted therapeutics and diagnostics, and provide mechanistic insights into other malignancies that arise within the context of microbially initiated inflammatory states.

1,719 citations

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TL;DR: It is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.
Abstract: Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.

1,450 citations