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Tobias baumgart

Conor M Haney, Christina L Cleveland, Rebecca F Wissner, Lily Owei, Jaclyn Robustelli, Malcolm J Daniels, Merve Canyurt, Priscilla Rodriguez, Harry Ischiropoulos, Tobias Baumgart, E James Petersson
Fibrillar aggregates of the protein α-synuclein (αS) are one of the hallmarks of Parkinson's disease. Here, we show that measuring the fluorescence polarization (FP) of labels at several sites on αS allows one to monitor changes in the local dynamics of the protein after binding to micelles or vesicles, and during fibril formation. Most significantly, these site-specific FP measurements provide insight into structural remodeling of αS fibrils by small molecules and have the potential for use in moderate-throughput screens to identify small molecules that could be used to treat Parkinson's disease...
November 11, 2016: Biochemistry
Ningwei Li, Nima Sharifi-Mood, Fuquan Tu, Daeyeon Lee, Ravi Radhakrishnan, Tobias Baumgart, Kathleen J Stebe
Inspired by proteins that generate membrane curvature, sense the underlying membrane geometry, and migrate driven by curvature gradients, we explore the question: Can colloids, adhered to lipid bilayers, also sense and respond to membrane geometry? We report the migration of Janus microparticles adhered to giant unilamellar vesicles elongated to present spatially varying curvatures. In our experiments, colloids migrate only when the membranes are tense, suggesting that they migrate to minimize membrane area...
December 30, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Zhiming Chen, Ehsan Atefi, Tobias Baumgart
Peripheral proteins can bend membranes through several different mechanisms, including scaffolding, wedging, oligomerization, and crowding. The crowding effect in particular has received considerable attention recently, in part because it is a colligative mechanism-implying that it could, in principle, be explored by any peripheral protein. Here we sought to clarify to what extent this mechanism is exploited by endocytic accessory proteins. We quantitatively investigate membrane curvature generation by means of a GUV shape stability assay...
November 1, 2016: Biophysical Journal
Zhiming Chen, Chen Zhu, Curtis J Kuo, Jaclyn Robustelli, Tobias Baumgart
N-BAR proteins such as endophilin are thought to bend lipid membranes via scaffolding (the molding of membranes through the crescent protein shape) and membrane insertion (also called wedging) of amphipathic helices. However, the contributions from these distinct mechanisms to membrane curvature generation and sensing have remained controversial. Here we quantitatively demonstrate that the amphipathic N-terminal H0 helix of endophilin is important for recruiting this protein to the membrane, but does not contribute significantly to its intrinsic membrane curvature generation capacity...
November 9, 2016: Journal of the American Chemical Society
Qi Xiao, Jack D Rubien, Zhichun Wang, Ellen H Reed, Daniel A Hammer, Dipankar Sahoo, Paul A Heiney, Srujana S Yadavalli, Mark Goulian, Samantha E Wilner, Tobias Baumgart, Sergei A Vinogradov, Michael L Klein, Virgil Percec
The modular synthesis of a library containing seven self-assembling amphiphilic Janus dendrimers is reported. Three of these molecules contain environmentally friendly chiral-racemic fluorinated dendrons in their hydrophobic part (RF), one contains achiral hydrogenated dendrons (RH), while one denoted hybrid Janus dendrimer, contains a combination of chiral-racemic fluorinated and achiral hydrogenated dendrons (RHF) in its hydrophobic part. Two Janus dendrimers contain either chiral-racemic fluorinated dendrons and a green fluorescent dye conjugated to its hydrophilic part (RF-NBD) or achiral hydrogenated and a red fluorescent dye in its hydrophilic part (RH-RhB)...
September 28, 2016: Journal of the American Chemical Society
Xingfeng Liu, Jisen Huai, Heiko Endle, Leslie Schlüter, Wei Fan, Yunbo Li, Sebastian Richers, Hajime Yurugi, Krishnaraj Rajalingam, Haichao Ji, Hong Cheng, Benjamin Rister, Guilherme Horta, Jan Baumgart, Hendrik Berger, Gregor Laube, Ulrich Schmitt, Michael J Schmeisser, Tobias M Boeckers, Stefan Tenzer, Andreas Vlachos, Thomas Deller, Robert Nitsch, Johannes Vogt
Alterations in dendritic spine numbers are linked to deficits in learning and memory. While we previously revealed that postsynaptic plasticity-related gene 1 (PRG-1) controls lysophosphatidic acid (LPA) signaling at glutamatergic synapses via presynaptic LPA receptors, we now show that PRG-1 also affects spine density and synaptic plasticity in a cell-autonomous fashion via protein phosphatase 2A (PP2A)/β1-integrin activation. PRG-1 deficiency reduces spine numbers and β1-integrin activation, alters long-term potentiation (LTP), and impairs spatial memory...
August 8, 2016: Developmental Cell
Qingjie Luo, Zheng Shi, Yitao Zhang, Xi-Jun Chen, Seo-Yeon Han, Tobias Baumgart, David M Chenoweth, So-Jung Park
Here, we report DNA-induced polymer segregation and DNA island formation in binary block copolymer assemblies. A DNA diblock copolymer of polymethyl acrylate-block-DNA (PMA-b-DNA) and a triblock copolymer of poly(butadiene)-block-poly(ethylene oxide)-block-DNA (PBD-b-PEO-b-DNA) were synthesized, and each was coassembled with a prototypical amphiphilic polymer of poly(butadiene)-block-poly(ethylene oxide) (PBD-b-PEO). The binary self-assembly of PMA-b-DNA and PBD-b-PEO resulted in giant polymersomes with DNA uniformly distributed in the hydrophilic PEO shell...
August 17, 2016: Journal of the American Chemical Society
Richard W Tourdot, N Ramakrishnan, Tobias Baumgart, Ravi Radhakrishnan
This corrects the article DOI: 10.1103/PhysRevE.92.042715.
May 2016: Physical Review. E
Richard W Tourdot, N Ramakrishnan, Tobias Baumgart, Ravi Radhakrishnan
We investigate the phenomenon of protein-induced tubulation of lipid bilayer membranes within a continuum framework using Monte Carlo simulations coupled with the Widom insertion technique to compute excess chemical potentials. Tubular morphologies are spontaneously formed when the density and the curvature-field strength of the membrane-bound proteins exceed their respective thresholds and this transition is marked by a sharp drop in the excess chemical potential. We find that the planar to tubular transition can be described by a micellar model and that the corresponding free-energy barrier increases with an increase in the curvature-field strength (i...
October 2015: Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics
Zhiming Chen, Zheng Shi, Tobias Baumgart
I-BAR proteins are well-known actin-cytoskeleton adaptors and have been observed to be involved in the formation of plasma membrane protrusions (filopodia). I-BAR proteins contain an all-helical, crescent-shaped IRSp53-MIM domain (IMD) dimer that is believed to be able to couple with a membrane shape. This coupling could involve the sensing and even the generation of negative plasma membrane curvature. Indeed, the in vitro studies have shown that IMDs can induce inward tubulation of liposomes. While N-BAR domains, which generate positive membrane curvature, have received a considerable amount of attention from both theory and experiments, the mechanisms of curvature coupling through IMDs are comparatively less studied and understood...
July 21, 2015: Biophysical Journal
Zheng Shi, Jonathan N Sachs, Elizabeth Rhoades, Tobias Baumgart
α-Synuclein is an intrinsically disordered protein whose aggregation is a hallmark of Parkinson's disease. In neurons, α-synuclein is thought to play important roles in mediating both endo- and exocytosis of synaptic vesicles through interactions with either the lipid bilayer or other proteins. Upon membrane binding, the N-terminus of α-synuclein forms a helical structure and inserts into the hydrophobic region of the outer membrane leaflet. However, membrane structural changes induced by α-synuclein are still largely unclear...
June 28, 2015: Physical Chemistry Chemical Physics: PCCP
Zheng Shi, Tobias Baumgart
Endocytosis is a ubiquitous eukaryotic membrane budding, vesiculation and internalization process fulfilling numerous roles including compensation of membrane area increase after bursts of exocytosis. The mechanism of the coupling between these two processes to enable homeostasis is not well understood. Recently, an ultrafast endocytosis (UFE) pathway was revealed with a speed significantly exceeding classical clathrin-mediated endocytosis (CME). Membrane tension reduction is a potential mechanism by which endocytosis can be rapidly activated at remote sites...
2015: Nature Communications
Roland L Knorr, Hitoshi Nakatogawa, Yoshinori Ohsumi, Reinhard Lipowsky, Tobias Baumgart, Rumiana Dimova
Autophagy is a cellular degradation pathway involving the shape transformation of lipid bilayers. During the onset of autophagy, the water-soluble protein Atg8 binds covalently to phosphatdylethanolamines (PEs) in the membrane in an ubiquitin-like reaction coupled to ATP hydrolysis. We reconstituted the Atg8 conjugation system in giant and nm-sized vesicles with a minimal set of enzymes and observed that formation of Atg8-PE on giant vesicles can cause substantial tubulation of membranes even in the absence of Atg12-Atg5-Atg16...
2014: PloS One
Ute Distler, Michael J Schmeisser, Assunta Pelosi, Dominik Reim, Jörg Kuharev, Roland Weiczner, Jan Baumgart, Tobias M Boeckers, Robert Nitsch, Johannes Vogt, Stefan Tenzer
Located at neuronal terminals, the postsynaptic density (PSD) is a highly complex network of cytoskeletal scaffolding and signaling proteins responsible for the transduction and modulation of glutamatergic signaling between neurons. Using ion-mobility enhanced data-independent label-free LC-MS/MS, we established a reference proteome of crude synaptosomes, synaptic junctions, and PSD derived from mouse hippocampus including TOP3-based absolute quantification values for identified proteins. The final dataset across all fractions comprised 49 491 peptides corresponding to 4558 protein groups...
November 2014: Proteomics
Hongying Shen, Francesca Giordano, Yumei Wu, Jason Chan, Chen Zhu, Ira Milosevic, Xudong Wu, Kai Yao, Bo Chen, Tobias Baumgart, Derek Sieburth, Pietro De Camilli
Genetic studies have suggested a functional link between cholesterol/sphingolipid metabolism and endocytic membrane traffic. Here we show that perturbing the cholesterol/sphingomyelin balance in the plasma membrane results in the massive formation of clusters of narrow endocytic tubular invaginations positive for N-BAR proteins. These tubules are intensely positive for sphingosine kinase 1 (SPHK1). SPHK1 is also targeted to physiologically occurring early endocytic intermediates, and is highly enriched in nerve terminals, which are cellular compartments specialized for exo/endocytosis...
July 2014: Nature Cell Biology
Tingting Wu, Zheng Shi, Tobias Baumgart
The regulation of membrane shapes is central to many cellular phenomena. Bin/Amphiphysin/Rvs (BAR) domain-containing proteins are key players for membrane remodeling during endocytosis, cell migration, and endosomal sorting. BIN1, which contains an N-BAR domain, is assumed to be essential for biogenesis of plasma membrane invaginations (T-tubules) in muscle tissues. Three mutations, K35N, D151N and R154Q, have been discovered so far in the BAR domain of BIN1 in patients with centronuclear myopathy (CNM), where impaired organization of T-tubules has been reported...
2014: PloS One
Zhiming Chen, Ken Chang, Benjamin R Capraro, Chen Zhu, Chih-Jung Hsu, Tobias Baumgart
Endophilin A1 is a homodimeric membrane-binding endocytic accessory protein with a high dimerization affinity. Its function has been hypothesized to involve autoinhibition. However, the autoinhibition mechanism, as well as the physicochemical basis for the high dimerization affinity of endophilin in solution, have remained unclear. In this contribution, we use a Förster resonance energy transfer (FRET) method to investigate the homodimerization mechanism and intradimer molecular interactions in endophilin...
March 26, 2014: Journal of the American Chemical Society
Zheng Shi, Tobias Baumgart
Biological membranes undergo constant shape remodeling involving the formation of highly curved structures. The lipid bilayer represents the fundamental architecture of the cellular membrane with its shapes determined by the Helfrich curvature bending energy. However, the dynamics of bilayer shape transitions, especially their modulation by membrane proteins, and the resulting shape instabilities, are still not well understood. Here, we review in a unifying manner several theories that describe the fluctuations (i...
June 2014: Advances in Colloid and Interface Science
Tobias Teismann, Eva-Maria A D Förtsch, Patrick Baumgart, Serkan Het, Johannes Michalak
The interpersonal theory of suicidal behavior proposes that fearlessness of death and physical pain insensitivity is a necessary requisite for self-inflicted lethal self-harm. Repeated experiences with painful and provocative events are supposed to cause an incremental increase in acquired capability. The present study examined whether playing a first-person shooter-game in contrast to a first-person racing game increases pain tolerance, a dimension of the acquired capability construct, and risk-taking behavior, a risk factor for developing acquired capability...
January 30, 2014: Psychiatry Research
Marcello Cavallaro, Mohamed A Gharbi, Daniel A Beller, Simon Čopar, Zheng Shi, Tobias Baumgart, Shu Yang, Randall D Kamien, Kathleen J Stebe
We exploit the long-ranged elastic fields inherent to confined nematic liquid crystals (LCs) to assemble colloidal particles trapped at the LC interface into reconfigurable structures with complex symmetries and packings. Spherical colloids with homeotropic anchoring trapped at the interface between air and the nematic LC 4-cyano-4'-pentylbiphenyl create quadrupolar distortions in the director field causing particles to repel and consequently form close-packed assemblies with a triangular habit. Here, we report on complex open structures organized via interactions with defects in the bulk...
November 19, 2013: Proceedings of the National Academy of Sciences of the United States of America
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