Regulation of molecular motor proteins (2023)

  • Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

    2015, Physics Reports

    Citation Excerpt :

    We shall also briefly address the case of some myosins able to carry cargos along actin filaments. The kinesin superfamily is subdivided into several tens of kinesin families [67] which exhibit surprisingly similar motor domains and therefore are all able to exert force on MTs [68]. Due to the remaining differences in the structure of the molecule, motion patterns vary: While most of the kinesins move toward the plus-end of a MT (anterograde movement), some kinesins move in the opposite or retrograde direction.

    Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized.

    The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach.

    It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer.

    We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal transport, because of its relevance for neuronal diseases. Some important characteristics of axonal transport is that it takes place in a confined environment; besides several types of motors are involved, that move in opposite directions. It is a challenge to understand how this bidirectional transport is organized. We review several features that could contribute to the efficiency of bidirectional transport in the axon, including in particular the role of motor–motor interactions and of the dynamics of the underlying microtubule network. Finally, we also discuss some open questions that may be relevant for future research in this field.

  • Stochastic mechano-chemical kinetics of molecular motors: A multidisciplinary enterprise from a physicist's perspective

    2013, Physics Reports

    Citation Excerpt :

    Modeling the determinants of the directionality and processivity of the different families of the same superfamily [564] cannot be done satisfactorily without incorporating the specific distinct features of the different families of motors. In this section we focus on the operational mechanism of a single motor taking into account its architectural design, the energetics of its interaction with the track and that with the fuel molecule, its mechano-chemical kinetic pathways as well as the mechanisms of their regulation and control [19,20,565–576]. Intracellular motor-driven transport [577] is a crucially important process not only for the maintenance of the cell, but also for its morphogenesis.

    A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors “transduce” input energy into mechanical work. All the nano-motors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We review not only the structural design and stochastic kinetics of individual single motors, but also their coordination, cooperation and competition as well as the assembly of multi-module motors in various intracellular kinetic processes. Although all the motors considered here execute mechanical movements, efficiency and power output are not necessarily good measures of performance of some motors. Among the intracellular nano-motors, we consider the porters, sliders and rowers, pistons and hooks, exporters, importers, packers and movers as well as those that also synthesize, manipulate and degrade “macromolecules of life”. We review mostly the quantitative models for the kinetics of these motors. We also describe several of those motor-driven intracellular stochastic processes for which quantitative models are yet to be developed. In part I, we discuss mainly the methodology and the generic models of various important classes of molecular motors. In part II, we review many specific examples emphasizing the unity of the basic mechanisms as well as diversity of operations arising from the differences in their detailed structure and kinetics. Multi-disciplinary research is presented here from the perspective of physicists.

  • Modeling of pattern regulation in melanophores

    2007, Journal of Theoretical Biology

    Melanosomes, pigment granules in melanophores, play a principal role in physiological color adaptation of fish and frog. Melanophores regulate melanosome trafficking on cytoskeletal filaments to generate a range of spatiotemporal patterns. Here, we present the first comprehensive model of spatiotemporal evolution of melanosome patterns. The model encompasses both physical and biochemical aspects of melanosome dynamics. It consists of (i) a kinetic description of biochemical reactions involved in intracellular signaling, (ii) a system of macroscopic reaction–diffusion–convection equations for melanosome concentration, and (iii) a set of constitutive relationships for coupling transport with the biochemical network. The model relates molecular-level regulatory actions to cell-level melanosome distribution, allowing unification of existing experimental observations and qualitative hypotheses into an integrated, consistent framework. The model reproduces salient features of melanosome patterns, both during transient and steady state. It gives useful insights into how cells coordinate motor-assisted transport to maintain and adapt spatial organization of intracellular organelles. In particular, we calculate the optimal transition paths from aggregation to dispersion in fish melanophores. The calculations suggest that fish melanophores optimally control intracellular signaling to maximize the efficiency of motor-assisted transport during dispersion.

  • Mitochondrial trafficking and morphology in healthy and injured neurons

    2006, Progress in Neurobiology

    Mitochondria are the primary generators of ATP and are important regulators of intracellular calcium homeostasis. These organelles are dynamically transported along lengthy neuronal processes, presumably for appropriate distribution to cellular regions of high metabolic demand and elevated intracellular calcium, such as synapses. The removal of damaged mitochondria that produce harmful reactive oxygen species and promote apoptosis is also thought to be mediated by transport of mitochondria to autophagosomes. Mitochondrial trafficking is therefore important for maintaining neuronal and mitochondrial health while cessation of movement may lead to neuronal and mitochondrial dysfunction. Mitochondrial morphology is also dynamic and is remodeled during neuronal injury and disease. Recent studies reveal different manifestations and mechanisms of impaired mitochondrial movement and altered morphology in injured neurons. These are likely to cause varied courses toward neuronal degeneration and death. The goal of this review is to provide an appreciation of the full range of mitochondrial function, morphology and trafficking, and the critical role these parameters play in neuronal physiology and pathophysiology.

  • Mitosis-specific kinesins in Arabidopsis

    2006, Trends in Plant Science

    Kinesins are a class of microtubule-associated proteins that posses a motor domain for binding to microtubules and, in general, allows movement along microtubules. In animal mitosis, they function in spindle formation, chromosome movement and in cytokinesis. In addition to the spindle, plants develop a preprophase band and a phragmoplast that might require multiple kinesins for construction and functioning. Indeed, several kinesins play a role in phragmoplast and cell plate dynamics. Surprisingly few kinesins have been associated with the spindle and the preprophase band. Analysis of expression datasets from synchronized cell cultures indicate that at least 23 kinesins are in some way implicated in mitosis-related processes. In this review, the function of kinesins in animal and plant mitoses are compared, and the divergence that originates from plant-specific aspects is highlighted.

  • Multiscale trend analysis of microtubule transport in melanophores

    2005, Biophysical Journal

    Citation Excerpt :

    As a result, MT-based transport is discontinuous and involves transitions between the three states—displacements to MT plus or minus ends and pauses (Gross et al., 2002; Morris and Hollenbeck, 1993; Welte et al., 1998). Net direction of the movement is regulated by second messengers such as cAMP or Ca2+ ions (reviewed in Reilein et al., 2001). Changes in the movement parameters that are induced by variations in the second-messenger levels are cell type-specific.

    Microtubule-based transport is critical for trafficking of organelles, organization of endomembranes, and mitosis. The driving force for microtubule-based transport is provided by microtubule motors, which move organelles specifically to the plus or minus ends of the microtubules. Motor proteins of opposite polarities are bound to the surface of the same cargo organelle. Transport of organelles along microtubules is discontinuous and involves transitions between movements to plus or minus ends or pauses. Parameters of the movement, such as velocity and length of runs, provide important information about the activity of microtubule motors, but measurement of these parameters is difficult and requires a sophisticated decomposition of the organelle movement trajectories into directional runs and pauses. The existing algorithms are based on establishing threshold values for the length and duration of runs and thus do not allow to distinguish between slow runs and pauses, making the analysis of the organelle transport incomplete. Here we describe a novel algorithm based on multiscale trend analysis for the decomposition of organelle trajectories into plus- or minus-end runs, and pauses. This algorithm is self-adapted to the characteristic durations and velocities of runs, and allows reliable separation of pauses from runs. We apply the proposed algorithm to compare regulation of microtubule transport in fish and Xenopus melanophores and show that the general mechanisms of regulation are similar in the two pigment cell types.

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  • Research article

    Effects of different spray formulations on the reproductive parameters of engorged Rhipicephalus (Boophilus) microplus females detached from experimentally infested cattle

    Preventive Veterinary Medicine, Volume 122, Issues 1–2, 2015, pp. 70-75

    This present study aimed to evaluate the deleterious effects of some commercially available spray formulations (15% Cypermethrin+25% Chlorpyriphos+1% Citronellal and 8% Cypermethrin+60% Ethion) on the reproductive parameters of engorged Rhipicephalus (Boophilus) microplus females that detached from experimentally infested cattle. The following reproductive parameters of engorged female ticks were analyzed: female weight, egg mass weight, percentage of hatchability, percentage of reduction in oviposition, percentage of reduction in hatchability, reproductive efficiency and percent control/efficacy of formulations for reproductive parameters. Our findings showed that although the strain R. (B.) microplus used in both experiments was thought to be sensitive to the test compounds because of the acaricidal efficacy observed throughout these trials, it was not possible to observe overall deleterious effects on the reproductive parameters of this tick species with both spray formulations. However, the 8% Cypermethrin+60% Ethion showed short-term significant effects on the weight of female ticks between the 14th and 16th days post-treatment and the weight of female and the egg mass weight between the 20th and 22nd days post-treatment. New studies should be conducted to show if these results regarding the reproductive parameters of fully engorged R. (B.) microplus females, combined with the acaricidal efficacy can be sufficient to reduce the number of chemical treatments administered to cattle.

  • Research article

    Surface characterization, electrochemical behaviour and cytotoxicity of UNS S31254 stainless steel for orthopaedic applications

    Materials Letters, Volume 148, 2015, pp. 71-75

    The surface characterization and electrochemical behaviour of UNS S31254 (254 SS) have been performed in 0.15molL−1 NaCl medium in order to evaluate its application as orthopaedic implants. Polarization curves, chronoamperometry, electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy were used for characterizing the samples. A cytotoxicity test was also performed to study the biocompatibility of the proposed steel as biomaterial. The electrochemical behaviour of 254 SS was compared to that observed for ISO 5832-9 and ASTM F138 stainless steels, used in orthopaedic implants. 254 SS is similar to ISO 5832-9 SS: it is passivated on the potential range between the corrosion and the transpassivation potential. Mo (VI) forms an outer layer which blocks Cr (VI) dissolution. Cytotoxicity test showed no cytotoxic character of 254 SS.

  • Research article

    The biology of Trichogramma pretiosum as atmospheric O2 becomes depleted and CO2 accumulates

    Biological Control, Volume 105, 2017, pp. 1-5

    This study evaluated the effect of modified atmospheric concentrations of O2 and CO2 on the biology of Trichogramma pretiosum Riley. For this purpose, cards with five different quantities of parasitized eggs were kept in hermetically sealed vials producing five different atmospheres as a function of different parasitoid respiration levels. Controls consisted of egg cards kept in an ambient atmosphere in ventilated vials. Concentrations of O2 and CO2 in vials were measured daily with a gas analyzer. No parasitoids emerged from vials where the CO2 concentration exceeded 16% and O2 was less than 2.5%. Only 47% of T. pretiosum emerged in an atmosphere with a maximum of 13.3% CO2 and 6.78% O2, significantly lower than in treatments with lower CO2 and higher O2 concentrations, or controls. Parasitoid performance was also diminished by high CO2 and low O2 conditions, relative to controls. We conclude that rearing conditions for T. pretiosum should ensure ventilation sufficient to maintain CO2 levels below 4.3% and O2 levels above 18.5%.

  • Research article

    Abnormal movement of tropomyosin and response of myosin heads and actin during the ATPase cycle caused by the Arg167His, Arg167Gly and Lys168Glu mutations in TPM1 gene

    Archives of Biochemistry and Biophysics, Volume 606, 2016, pp. 157-166

    Amino acid substitutions: Arg167His, Arg167Gly and Lys168Glu, located in a consensus actin-binding site of the striated muscle tropomyosin Tpm1.1 (TM), were used to investigate mechanisms of the thin filament regulation. The azimuthal movement of TM strands on the actin filament and the responses of the myosin heads and actin subunits during the ATPase cycle were studied using fluorescence polarization of muscle fibres. The recombinant wild-type and mutant TMs labelled with 5-IAF, 1,5-IAEDANS-labelled S1and FITC-phalloidin F-actin were incorporated into the ghost muscle fibres to acquire information on the orientation of the probes relative to the fibre axis. The substitutions Arg167Gly and Lys168Glu shifted TM strands into the actin filament centre, whereas Arg167His moved TM towards the periphery of the filament. In the presence of Arg167Gly-TM and Lys168Glu-TM the fraction of actin monomers that were switched on and the number of the myosin heads strongly bound to F-actin were abnormally high even under conditions close to relaxation. In contrast, Arg167His-TM decreased the fraction of switched on actin and reduced the formation of strongly bound myosin heads throughout the ATPase cycle. We concluded that the altered TM-actin contacts destabilized the thin filament and affected the actin-myosin interactions.

  • Research article

    Favorable effects of ezetimibe alone or in association with simvastatin on the removal from plasma of chylomicrons in coronary heart disease subjects

    Atherosclerosis, Volume 233, Issue 1, 2014, pp. 319-325

    Reductions on the clearance from plasma of chylomicrons are associated with atherosclerosis. Statins improve the removal from plasma of chylomicrons in a dose dependent manner. There is controversy whether ezetimibe modifies the plasma clearance of chylomicrons. Effects of ezetimibe alone or in combination with simvastatin were compared with low and high dose of the latter, upon the kinetics of a chylomicron-like emulsion in coronary heart disease (CHD) patients.

    25 CHD patients were randomized for treatment with ezetimibe 10mg (group 1) or simvastatin 20mg (group 2) with progression to ezetimibe+simvastatin 10/20mg or simvastatin 80mg, respectively. Kinetic studies were performed at baseline and after each treatment period of 6 weeks. The fractional catabolic rates (FCR) of the emulsion labeled with 14C-CE and 3H-TG, that represent respectively chylomicron remnant and triglyceride removal, were calculated. Comparisons were made by ANOVA.

    The 14CE-FCR in group 1 were 0.005±0.004, 0.011±0.008 and 0.018±0.005min−1 and in group 2 were 0.004±0.003, 0.011±0.008 and 0.019±0.007min−1 respectively at baseline, after 6 and 12 weeks (p<0.05 vs. baseline, and 6 vs. 12 weeks). The 3H-TG-FCR in group 1 were 0.017±0.011, 0.024±0.011 and 0.042±0.013min−1 and in group 2 were 0.016±0.009, 0.022±0.009 and 0.037±0.012min−1 at baseline, after 6 and 12 weeks (p<0.05 vs. baseline, and 6 vs. 12 weeks). There were no differences between groups in time.

    Both treatments increased similarly the removal from plasma of chylomicron and remnants in CHD patients.

  • Research article

    Troponin-like regulation in muscle thin filaments of the mussel Crenomytilus grayanus (Bivalvia: Mytiloida)

    Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Volume 1854, Issue 10, Part A, 2015, pp. 1444-1450

    Muscles of bivalve molluscs have double calcium regulation — myosin-linked and actin-linked. While the mechanism of myosin-linked regulation is sufficiently studied, there is still no consensus on the mechanism of actin-linked regulation. Earlier we showed a high degree of Ca2+-sensitivity of thin filaments from the adductor muscle of the mussel Crenomytilus grayanus (Mytiloida). In order to elucidate the nature of this regulation, we isolated the fraction of minor proteins from the mussel thin filaments, which confers Ca2+-sensitivity to reconstituted actomyosin–tropomyosin. Proteins of this fraction, ABP-19, ABP-20, and ABP-28, were chromatographically purified and identified. According to the results of mass spectrometry and Western blot analysis, as well as by their functional properties, these mussel actin-binding proteins appeared to correspond to the troponin components from the skeletal muscles of vertebrates (TnC, TnI and TnT). The reconstituted mussel troponin complex confers to actomyosin–tropomyosin more than 80% Ca2+-sensitivity. The in vivo molar ratio of actin/tropomyosin/troponin was calculated to be 7:1:0.5, i.e., the content of troponin in mussel thin filaments is two times lower than in thin filaments of skeletal muscles of vertebrates. These data demonstrate that troponin-like regulation found in the catch muscle of the mussel C. grayanus is present at least in two suborders of bivalves: Pectinoida and Mytiloida.

Copyright © 2001 Published by Elsevier Inc.

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