The Experts below are selected from a list of 76500 Experts worldwide ranked by ideXlab platform
Jonathan M. Scholey - One of the best experts on this subject based on the ideXlab platform.
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kinesin 2 a family of heterotrimeric and homodimeric motors with diverse Intracellular Transport functions
Annual Review of Cell and Developmental Biology, 2013Co-Authors: Jonathan M. ScholeyAbstract:Kinesin-2 was first purified as a heterotrimeric, anterograde, microtubule-based motor consisting of two distinct kinesin-related subunits and a novel associated protein (KAP) that is currently best known for its role in intraflagellar Transport and ciliogenesis. Subsequent work, however, has revealed diversity in the oligomeric state of different kinesin-2 motors owing to the combinatorial heterodimerization of its subunits and the coexistence of both heterotrimeric and homodimeric kinesin-2 motors in some cells. Although the functional significance of the homo- versus heteromeric organization of kinesin-2 motor subunits and the role of KAP remain uncertain, functional studies suggest that cooperation between different types of kinesin-2 motors or between kinesin-2 and a member of a different motor family can generate diverse patterns of anterograde Intracellular Transport. Moreover, despite being restricted to ciliated eukaryotes, kinesin-2 motors are now known to drive diverse Transport events outside ...
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kinesin 2 a family of heterotrimeric and homodimeric motors with diverse Intracellular Transport functions
Annual Review of Cell and Developmental Biology, 2013Co-Authors: Jonathan M. ScholeyAbstract:Kinesin-2 was first purified as a heterotrimeric, anterograde, microtubule-based motor consisting of two distinct kinesin-related subunits and a novel associated protein (KAP) that is currently best known for its role in intraflagellar Transport and ciliogenesis. Subsequent work, however, has revealed diversity in the oligomeric state of different kinesin-2 motors owing to the combinatorial heterodimerization of its subunits and the coexistence of both heterotrimeric and homodimeric kinesin-2 motors in some cells. Although the functional significance of the homo- versus heteromeric organization of kinesin-2 motor subunits and the role of KAP remain uncertain, functional studies suggest that cooperation between different types of kinesin-2 motors or between kinesin-2 and a member of a different motor family can generate diverse patterns of anterograde Intracellular Transport. Moreover, despite being restricted to ciliated eukaryotes, kinesin-2 motors are now known to drive diverse Transport events outside cilia. Here, I review the organization, assembly, phylogeny, biological functions, and motility mechanism of this diverse family of Intracellular Transport motors.
Patrick Borel - One of the best experts on this subject based on the ideXlab platform.
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proteins involved in uptake Intracellular Transport and basolateral secretion of fat soluble vitamins and carotenoids by mammalian enterocytes
Progress in Lipid Research, 2011Co-Authors: Emmanuelle Reboul, Patrick BorelAbstract:Our understanding of the molecular mechanisms responsible for fat-soluble vitamin uptake and Transport at the intestinal level has advanced considerably over the past decade. On one hand, it has long been considered that vitamin D and E as well as β-carotene (the main provitamin A carotenoid in human diet) were absorbed by a passive diffusion process, although this could not explain the broad inter-individual variability in the absorption efficiency of these molecules. On the other hand, it was assumed that preformed vitamin A (retinol) and vitamin K1 (phylloquinone) absorption occurred via energy-dependent processes, but the Transporters involved have not yet been identified. The recent discovery of intestinal proteins able to facilitate vitamin E and carotenoid uptake and secretion by the enterocyte has spurred renewed interest in studying the fundamental mechanisms involved in the absorption of these micronutrients. The proteins identified so far are cholesterol Transporters such as SR-BI (scavenger receptor class B type I), CD36 (cluster determinant 36), NPC1L1 (Niemann-Pick C1-like 1) or ABCA1 (ATP-Binding Cassette A1) displaying a broad substrate specificity, but it is likely that other membrane proteins are also involved. After overviewing the metabolism of fat-soluble vitamins and carotenoids in the human upper gastrointestinal lumen, we will focus on the putative or identified proteins participating in the intestinal uptake, Intracellular Transport and basolateral secretion of these fat-soluble vitamins and carotenoids, and outline the uncertainties that need to be explored in the future. Identifying the proteins involved in intestinal uptake and Transport of fat-soluble vitamins and carotenoids across the enterocyte is of great importance, especially as some of them are already targets for the development of drugs able to slow cholesterol absorption. Indeed, these drugs may also interfere with lipid vitamin uptake. A better understanding of the molecular mechanisms involved in fat-soluble vitamin and carotenoid absorption is a priority to better optimize their bioavailability.
Nickolay Korabel - One of the best experts on this subject based on the ideXlab platform.
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deciphering anomalous heterogeneous Intracellular Transport with neural networks
eLife, 2020Co-Authors: Daniel Han, Nickolay Korabel, Runze Chen, Mark Johnston, Anna Gavrilova, Victoria J Allan, Sergei Fedotov, Thomas A WaighAbstract:Intracellular Transport is predominantly heterogeneous in both time and space, exhibiting varying non-Brownian behavior. Characterization of this movement through averaging methods over an ensemble of trajectories or over the course of a single trajectory often fails to capture this heterogeneity. Here, we developed a deep learning feedforward neural network trained on fractional Brownian motion, providing a novel, accurate and efficient method for resolving heterogeneous behavior of Intracellular Transport in space and time. The neural network requires significantly fewer data points compared to established methods. This enables robust estimation of Hurst exponents for very short time series data, making possible direct, dynamic segmentation and analysis of experimental tracks of rapidly moving cellular structures such as endosomes and lysosomes. By using this analysis, fractional Brownian motion with a stochastic Hurst exponent was used to interpret, for the first time, anomalous Intracellular dynamics, revealing unexpected differences in behavior between closely related endocytic organelles.
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deciphering anomalous heterogeneous Intracellular Transport with neural networks
bioRxiv, 2019Co-Authors: Daniel Han, Nickolay Korabel, Runze Chen, Mark Johnston, Victoria J Allan, Sergei Fedotov, Thomas A WaighAbstract:Biological Intracellular Transport is predominantly heterogeneous in both time and space, exhibiting varying non-Brownian behaviour. Characterisation of this movement through averaging methods over an ensemble of trajectories or over the course of a single trajectory often fails to capture this heterogeneity adequately. Here, we have developed a deep learning feedforward neural network trained on fractional Brownian motion, which provides a novel, accurate and efficient characterization method for resolving heterogeneous behaviour of Intracellular Transport both in space and time. Importantly, the neural network requires significantly fewer data points compared to established methods, such as mean square displacements, rescaled range analysis and sequential range analysis. This enables robust estimation of Hurst exponents for very short time series data, making possible direct, dynamic segmentation and analysis of experimental tracks of rapidly moving cellular structures such as endosomes and lysosomes. By using this analysis, we were able to interpret anomalous Intracellular dynamics as fractional Brownian motion with a stochastic Hurst exponent.
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cytoskeletal network morphology regulates Intracellular Transport dynamics
Biophysical Journal, 2015Co-Authors: David Ando, Nickolay Korabel, Kerwyn Casey Huang, Ajay GopinathanAbstract:Intracellular Transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active Transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active Transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based Transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate Transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular Transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network Transport. Filament polarity was more important than filament orientation in reducing average transit times, and Transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on Intracellular Transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational Transport network design.
Thomas A Waigh - One of the best experts on this subject based on the ideXlab platform.
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deciphering anomalous heterogeneous Intracellular Transport with neural networks
eLife, 2020Co-Authors: Daniel Han, Nickolay Korabel, Runze Chen, Mark Johnston, Anna Gavrilova, Victoria J Allan, Sergei Fedotov, Thomas A WaighAbstract:Intracellular Transport is predominantly heterogeneous in both time and space, exhibiting varying non-Brownian behavior. Characterization of this movement through averaging methods over an ensemble of trajectories or over the course of a single trajectory often fails to capture this heterogeneity. Here, we developed a deep learning feedforward neural network trained on fractional Brownian motion, providing a novel, accurate and efficient method for resolving heterogeneous behavior of Intracellular Transport in space and time. The neural network requires significantly fewer data points compared to established methods. This enables robust estimation of Hurst exponents for very short time series data, making possible direct, dynamic segmentation and analysis of experimental tracks of rapidly moving cellular structures such as endosomes and lysosomes. By using this analysis, fractional Brownian motion with a stochastic Hurst exponent was used to interpret, for the first time, anomalous Intracellular dynamics, revealing unexpected differences in behavior between closely related endocytic organelles.
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deciphering anomalous heterogeneous Intracellular Transport with neural networks
bioRxiv, 2019Co-Authors: Daniel Han, Nickolay Korabel, Runze Chen, Mark Johnston, Victoria J Allan, Sergei Fedotov, Thomas A WaighAbstract:Biological Intracellular Transport is predominantly heterogeneous in both time and space, exhibiting varying non-Brownian behaviour. Characterisation of this movement through averaging methods over an ensemble of trajectories or over the course of a single trajectory often fails to capture this heterogeneity adequately. Here, we have developed a deep learning feedforward neural network trained on fractional Brownian motion, which provides a novel, accurate and efficient characterization method for resolving heterogeneous behaviour of Intracellular Transport both in space and time. Importantly, the neural network requires significantly fewer data points compared to established methods, such as mean square displacements, rescaled range analysis and sequential range analysis. This enables robust estimation of Hurst exponents for very short time series data, making possible direct, dynamic segmentation and analysis of experimental tracks of rapidly moving cellular structures such as endosomes and lysosomes. By using this analysis, we were able to interpret anomalous Intracellular dynamics as fractional Brownian motion with a stochastic Hurst exponent.
Nobutaka Hirokawa - One of the best experts on this subject based on the ideXlab platform.
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kinesin superfamily proteins kifs as a fundamental component of life Intracellular Transport and beyond
Reference Module in Biomedical Sciences#R##N#Encyclopedia of Cell Biology, 2016Co-Authors: Yosuke Tanaka, Nobutaka HirokawaAbstract:Intracellular Transport is an essential process for cellular functions and is driven by molecular motors. Kinesin superfamily proteins (KIFs) are a major superfamily of molecular motors that use the microtubule cytoskeleton. KIFs are encoded by more than 45 genes and perform fundamental functions that are necessary for life. Here, we summarize the history of and recent progress in KIF research in multiple disciplines, including molecular and cellular biology, molecular genetics, and structural biology, toward unraveling the roles and mechanisms of kinesin function. Some atypical roles of KIFs in signal transduction will also be discussed.
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Kinesin superfamily motor proteins and Intracellular Transport
Nature Reviews Molecular Cell Biology, 2009Co-Authors: Nobutaka Hirokawa, Yosuke Tanaka, Yasuko Noda, Shinsuke NiwaAbstract:Intracellular Transport is fundamental for cellular function, survival and morphogenesis. Kinesin superfamily proteins (also known as KIFs) are important molecular motors that directionally Transport various cargos, including membranous organelles, protein complexes and mRNAs. The mechanisms by which different kinesins recognize and bind to specific cargos, as well as how kinesins unload cargo and determine the direction of Transport, have now been identified. Furthermore, recent molecular genetic experiments have uncovered important and unexpected roles for kinesins in the regulation of such physiological processes as higher brain function, tumour suppression and developmental patterning. These findings open exciting new areas of kinesin research.
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Intracellular Transport and kinesin superfamily proteins kifs structure function and dynamics
Physical Review, 2008Co-Authors: Nobutaka Hirokawa, Yasuko NodaAbstract:Various molecular cell biology and molecular genetic approaches have indicated significant roles for kinesin superfamily proteins (KIFs) in Intracellular Transport and have shown that they are critical for cellular morphogenesis, functioning, and survival. KIFs not only Transport various membrane organelles, protein complexes, and mRNAs for the maintenance of basic cellular activity, but also play significant roles for various mechanisms fundamental for life, such as brain wiring, higher brain functions such as memory and learning and activity-dependent neuronal survival during brain development, and for the determination of important developmental processes such as left-right asymmetry formation and suppression of tumorigenesis. Accumulating data have revealed a molecular mechanism of cargo recognition involving scaffolding or adaptor protein complexes. Intramolecular folding and phosphorylation also regulate the binding activity of motor proteins. New techniques using molecular biophysics, cryoelectron microscopy, and X-ray crystallography have detected structural changes in motor proteins, synchronized with ATP hydrolysis cycles, leading to the development of independent models of monomer and dimer motors for processive movement along microtubules.