共查询到20条相似文献,搜索用时 31 毫秒
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R D Vale 《Trends in biochemical sciences》1992,17(8):300-304
A far greater variety of microtubule-based motors populate the interior of most eukaryotic cells than was ever imagined, and the inventory of these proteins is growing each year. The discovery of new motors, however, has raised many questions of how cells use their arsenal of force-generating machines. The ability to apply genetics, bacterial expression, biochemistry and in vitro motility assays to study motor proteins provides new opportunities for examining these problems at a molecular level. 相似文献
3.
Joshua S. Waitzman Sarah E. Rice 《Biology of the cell / under the auspices of the European Cell Biology Organization》2014,106(1):1-12
Mitotic cell division is the most fundamental task of all living cells. Cells have intricate and tightly regulated machinery to ensure that mitosis occurs with appropriate frequency and high fidelity. A core element of this machinery is the kinesin‐5 motor protein, which plays essential roles in spindle formation and maintenance. In this review, we discuss how the structural and mechanical properties of kinesin‐5 motors uniquely suit them to their mitotic role. We describe some of the small molecule inhibitors and regulatory proteins that act on kinesin‐5, and discuss how these regulators may influence the process of cell division. Finally, we touch on some more recently described functions of kinesin‐5 motors in non‐dividing cells. Throughout, we highlight a number of open questions that impede our understanding of both this motor's function and the potential utility of kinesin‐5 inhibitors. 相似文献
4.
Campàs O Leduc C Bassereau P Casademunt J Joanny JF Prost J 《Biophysical journal》2008,94(12):5009-5017
Intracellular transport relies on the action of motor proteins, which work collectively to either carry small vesicles or pull membranes tubes along cytoskeletal filaments. Although the individual properties of kinesin-1 motors have been extensively studied, little is known on how several motors coordinate their action and spatially organize on the microtubule when pulling on fluid membranes. Here we address these questions by studying, both experimentally and numerically, the growth of membrane tubes pulled by molecular motors. Our in vitro setup allows us to simultaneously control the parameters monitoring tube growth and measure its characteristics. We perform numerical simulations of membrane tube growth, using the experimentally measured values of all parameters, and analyze the growth properties of the tube considering various motor cooperation schemes. The comparison of the numerical results and the experimental data shows that motors use simultaneously several protofilaments of a microtubule to pull a single tube, as motors moving along a single protofilament cannot generate the forces required for tube extraction. In our experimental conditions, we estimate the average number of motors pulling the tube to be approximately nine, distributed over three contiguous protofilaments. Our results also indicate that the motors pulling the tube do not step synchronously. 相似文献
5.
It is now clear that transport on microtubules by dynein and kinesin family motors has an important if not critical role in the replication and spread of many different viruses. Understanding how viruses hijack dynein and kinesin motors using a limited repertoire of proteins offers a great opportunity to determine the molecular basis of motor recruitment. In this review, we discuss the interactions of dynein and kinesin-1 with adenovirus, the α herpes viruses: herpes simplex virus (HSV1) and pseudorabies virus (PrV), human immunodeficiency virus type 1 (HIV-1) and vaccinia virus. We highlight where the molecular links to these opposite polarity motors have been defined and discuss the difficulties associated with identifying viral binding partners where the basis of motor recruitment remains to be established. Ultimately, studying microtubule-based motility of viruses promises to answer fundamental questions as to how the activity and recruitment of the dynein and kinesin-1 motors are coordinated and regulated during bi-directional transport. 相似文献
6.
Making sense of melanosome dynamics in mouse melanocytes 总被引:4,自引:0,他引:4
Wu X Hammer JA 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2000,13(4):241-247
Molecular motors drive most if not all organelle movements in Eukaryotic cells. These proteins are thought to bind to the organelle surface and, through the action of their mechanochemical domains, to translocate the organelle along a cytoskeletal track. In the case of the myosin family of molecular motors, the cytoskeletal track is filamentous actin. Microtubules serve as the cytoskeletal track for the kinesins and dyneins. While a considerable amount is known about the motors and tracks responsible for the bi-directional movement of pigment granules in fish and frog melanophores, relatively little is known about how melanosomes in mammalian melanocytes are transported out the cells dendritic arbor, accumulated at the ends of these dendrites, and transferred to keratinocytes. In this short review, we focus on the use of video microscopy to address these questions in mouse melanocytes, and we describe how an analysis of melanosome dynamics within wild type and dilute melanocytes shaped our thinking regarding the role of an unconventional myosin in melanosome transport and distribution. 相似文献
7.
Members of the kinesin superfamily of microtubule-based motors and the myosin superfamily of actin-based motors that move 'backwards' have been identified. As the core catalytic domains of myosins and kinesins are similar in structure, this raises the intriguing questions of how direction reversal is accomplished and whether kinesins and myosins share mechanisms for switching their motors into reverse. 相似文献
8.
The bidirectional movement of intracellular cargo is usually described as a tug-of-war among opposite-directed families of molecular motors. While tug-of-war models have enjoyed some success, recent evidence suggests underlying motor interactions are more complex than previously understood. For example, these tug-of-war models fail to predict the counterintuitive phenomenon that inhibiting one family of motors can decrease the functionality of opposite-directed transport. In this paper, we use a stochastic differential equations modeling framework to explore one proposed physical mechanism, called microtubule tethering, that could play a role in this “co-dependence” among antagonistic motors. This hypothesis includes the possibility of a trade-off: weakly bound trailing molecular motors can serve as tethers for cargoes and processing motors, thereby enhancing motor–cargo run lengths along microtubules; however, this introduces a cost of processing at a lower mean velocity. By computing the small- and large-time mean-squared displacement of our theoretical model and comparing our results to experimental observations of dynein and its “helper protein” dynactin, we find some supporting evidence for microtubule tethering interactions. We extrapolate these findings to predict how dynein–dynactin might interact with the opposite-directed kinesin motors and introduce a criterion for when the trade-off is beneficial in simple systems. 相似文献
9.
Analysis of the myosins encoded in the recently completed Arabidopsis thaliana genome sequence 总被引:1,自引:0,他引:1
Background
Three types of molecular motors play an important role in the organization, dynamics and transport processes associated with the cytoskeleton. The myosin family of molecular motors move cargo on actin filaments, whereas kinesin and dynein motors move cargo along microtubules. These motors have been highly characterized in non-plant systems and information is becoming available about plant motors. The actin cytoskeleton in plants has been shown to be involved in processes such as transportation, signaling, cell division, cytoplasmic streaming and morphogenesis. The role of myosin in these processes has been established in a few cases but many questions remain to be answered about the number, types and roles of myosins in plants.Results
Using the motor domain of an Arabidopsis myosin we identified 17 myosin sequences in the Arabidopsis genome. Phylogenetic analysis of the Arabidopsis myosins with non-plant and plant myosins revealed that all the Arabidopsis myosins and other plant myosins fall into two groups - class VIII and class XI. These groups contain exclusively plant or algal myosins with no animal or fungal myosins. Exon/intron data suggest that the myosins are highly conserved and that some may be a result of gene duplication.Conclusions
Plant myosins are unlike myosins from any other organisms except algae. As a percentage of the total gene number, the number of myosins is small overall in Arabidopsis compared with the other sequenced eukaryotic genomes. There are, however, a large number of class XI myosins. The function of each myosin has yet to be determined. 相似文献10.
Messengers, motors and mysteries: sorting of eukaryotic mRNAs by cytoskeletal transport 总被引:1,自引:0,他引:1
Bullock SL 《Biochemical Society transactions》2011,39(5):1161-1165
It has become increasingly apparent in recent years that the subcellular localization of specific mRNAs is a prevalent method for spatially controlling gene expression. In most cases, targeting of mRNAs is mediated by transport along cytoskeletal filaments by molecular motors. However, the means by which specific messages are recognized and linked to the motors are poorly understood. Here, I will provide an overview of recent progress in elucidating the molecular mechanisms and principles of mRNA transport, including several studies highlighting the co-operation of different motors during the localization process. Important outstanding questions will also be highlighted. 相似文献
11.
DoHarris L Giesler A Humber B Sukumar A Janssen LJ 《Advances in physiology education》2011,35(2):213-218
A wide variety of cellular processes use molecular motors, including processive motors that move along some form of track (e.g., myosin with actin, kinesin or dynein with tubulin) and polymerases that move along a template (e.g., DNA and RNA polymerases, ribosomes). In trying to understand how these molecular motors actually move, many apply their understanding of how man-made motors work: the latter use some form of energy to exert a force or torque on its load. However, quite a different mechanism has been proposed to possibly account for the movement of molecular motors. Rather than hydrolyzing ATP to push or pull their load, they might use their own thermal vibrational energy as well as that of their load and their environment to move the load, capturing those movements that occur along a desired vector or axis and resisting others; ATP hydrolysis is required to make backward movements impossible. This intriguing thermal capture or Brownian ratchet model is relatively more difficult to convey to students. In this report, we describe several teaching aids that are very easily constructed using widely available household materials to convey the concept of a molecular ratchet. 相似文献
12.
The cytoskeleton and cardiac ion channel expression are closely linked. From the time that newly synthesized channels exit the endoplasmic reticulum, they are either traveling along the microtubule or actin cytoskeletons or likely anchored in the plasma membrane or in internal vesicular pools by those scaffolds. Molecular motors, small GTPases and even the dynamics of the cytoskeletons themselves influence the trafficking and expression of the channels. In some cases, the functioning of the channels themselves has profound influences on the cytoskeleton. Here we provide an overview of the current state of knowledge on the involvement of the actin and microtubule cytoskeletons in the trafficking, targeting and expression of cardiac ion channels and a few channels expressed elsewhere. We highlight, also, some of the many questions that remain about these processes. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé. 相似文献
13.
Background
Kinesin motors hydrolyze ATP to produce force and move along microtubules, converting chemical energy into work by a mechanism that is only poorly understood. Key transitions and intermediate states in the process are still structurally uncharacterized, and remain outstanding questions in the field. Perturbing the motor by introducing point mutations could stabilize transitional or unstable states, providing critical information about these rarer states. 相似文献14.
Recent research on kinesin motors has outlined the diversity of the superfamily and defined specific cargoes moved by kinesin family (KIF) members. Owing to the difficulty of purifying large amounts of native motors, much of this work has relied on recombinant proteins expressed in vitro. This approach does not allow ready determination of the complement of kinesin motors present in a given tissue, the relative amounts of different motors, or comparison of their native activities. To address these questions, we isolated nucleotide-dependent, microtubule-binding proteins from 13-day chick embryo brain. Proteins were enriched by microtubule affinity purification, then subjected to velocity sedimentation to separate the 20S dynein/dynactin pool from a slower sedimenting KIF containing pool. Analysis of the latter pool by anion exchange chromatography revealed three KIF species: kinesin I (KIF5), kinesin II (KIF3), and KIF1C (Unc104/KIF1). The most abundant species, kinesin I, exhibited the expected long range microtubule gliding activity. By contrast, KIF1C did not move microtubules. Kinesin II, the second most abundant KIF, could be fractionated into two pools, one containing predominantly A/B isoforms and the other containing A/C isoforms. The two motor species had similar activities, powering microtubule gliding at slower speeds and over shorter distances than kinesin I. 相似文献
15.
The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well. 相似文献
16.
Myosin VI is the only known molecular motor for the transportation of cargo vesicles from the plus end to the minus end of
actin filaments. Thus, myosin VI possesses several unique features to distinguish it from other myosin family motors, such
as the ability to move in a reverse direction, the unusual large walking step size, and the cargo-mediated dimerization. Recent
structural studies of myosin VI have provided mechanistic insights into these unique features. On the basis of the resolved
structures of myosin VI each domains (i.e., the structures of the N-terminal motor domain, the C-terminal cargo binding domain,
and the region in the middle), the unique features of myosin VI will be reviewed here from a structural perspective. The structural
studies of myosin VI definitely provide some answers about the unique features of myosin VI, but also raise significant questions
on how myosin VI functions as a special motor both for directional cargo transport and for structural anchoring. 相似文献
17.
Daniel Riveline 《Journal of nanobiotechnology》2013,11(Z1):S1
At scales below micrometers, Brownian motion dictates most of the behaviors. The simple observation of a colloid is striking: a permanent and random motion is seen, whereas inertial forces play a negligible role. This Physics, where velocity is proportional to force, has opened new horizons in biology. The random feature is challenged in living systems where some proteins - molecular motors - have a directed motion whereas their passive behaviors of colloid should lead to a Brownian motion. Individual proteins, polymers of living matter such as DNA, RNA, actin or microtubules, molecular motors, all these objects can be viewed as chains of colloids. They are submitted to shocks from molecules of the solvent. Shapes taken by these biopolymers or dynamics imposed by motors can be measured and modeled from single molecules to their collective effects. Thanks to the development of experimental methods such as optical tweezers, Atomic Force Microscope (AFM), micropipettes, and quantitative fluorescence (such as Förster Resonance Energy Transfer, FRET), it is possible to manipulate these individual biomolecules in an unprecedented manner: experiments allow to probe the validity of models; and a new Physics has thereby emerged with original biological insights. Theories based on statistical mechanics are needed to explain behaviors of these systems. When force-extension curves of these molecules are extracted, the curves need to be fitted with models that predict the deformation of free objects or submitted to a force. When velocity of motors is altered, a quantitative analysis is required to explain the motions of individual molecules under external forces. This lecture will give some elements of introduction to the lectures of the session 'Nanophysics for Molecular Biology'. 相似文献
18.
《Biophysical journal》2020,118(11):2703-2717
Molecular motors drive cytoskeletal rearrangements to change cell shape. Myosins are the motors that move, cross-link, and modify the actin cytoskeleton. The primary force generator in contractile actomyosin networks is nonmuscle myosin II (NMMII), a molecular motor that assembles into ensembles that bind, slide, and cross-link actin filaments (F-actin). The multivalence of NMMII ensembles and their multiple roles have confounded the resolution of crucial questions, including how the number of NMMII subunits affects dynamics and what affects the relative contribution of ensembles’ cross-linking versus motoring activities. Because biophysical measurements of ensembles are sparse, modeling of actomyosin networks has aided in discovering the complex behaviors of NMMII ensembles. Myosin ensembles have been modeled via several strategies with variable discretization or coarse graining and unbinding dynamics, and although general assumptions that simplify motor ensembles result in global contractile behaviors, it remains unclear which strategies most accurately depict cellular activity. Here, we used an agent-based platform, Cytosim, to implement several models of NMMII ensembles. Comparing the effects of bond type, we found that ensembles of catch-slip and catch motors were the best force generators and binders of filaments. Slip motor ensembles were capable of generating force but unbound frequently, resulting in slower contractile rates of contractile networks. Coarse graining of these ensemble types from two sets of 16 motors on opposite ends of a stiff rod to two binders, each representing 16 motors, reduced force generation, contractility, and the total connectivity of filament networks for all ensemble types. A parallel cluster model, previously used to describe ensemble dynamics via statistical mechanics, allowed better contractility with coarse graining, though connectivity was still markedly reduced for this ensemble type with coarse graining. Together, our results reveal substantial tradeoffs associated with the process of coarse graining NMMII ensembles and highlight the robustness of discretized catch-slip ensembles in modeling actomyosin networks. 相似文献
19.
Linda Wordeman 《Seminars in cell & developmental biology》2010,21(3):260-268
Kinesins are enzymes that use the energy of ATP to perform mechanical work. There are approximately 14 families of kinesins within the kinesin superfamily. Family classification is derived primarily from alignments of the sequences of the core motor domain. For this reason, the enzymatic behavior and motility of each motor generally reflects its family. At the cellular level, kinesin motors perform a variety of functions during cell division and within the mitotic spindle to ensure that chromosomes are segregated with the highest fidelity possible. The cellular functions of these motors are intimately related to their mechanical and enzymatic properties at the single molecule level. For this reason, motility studies designed to evaluate the activity of purified molecular motors are a requirement in order to understand, mechanistically, how these motors make the mitotic spindle work and what can cause the spindle to fail. This review will focus on a selection of illustrative kinesins, which have been studied at the molecular level in order to inform our understanding of their function in cells. In addition, the review will endeavor to point out some kinesins that have been studied extensively but which still lack sufficient molecular underpinnings to fully predict their contribution to spindle function. 相似文献
20.
Burkhardt JK 《Trends in cell biology》1996,6(4):127-131
The past few years have seen an explosion in the number of molecular motors reported in the literature. By us the energy of hydrolysis, these motors move various organelles along cytoskeletal 'tracks' within the cell. It is thought that some of the specificity of movement resides in receptors on the surface of the cargo organelles, but, in general, little is known about these molecules. In this article, Janis Burkhardt discusses the evidence that the protein kinectin serves as a membrane receptor for kinesin, and describes how motor-receptor proteins may interact with other components of the motility machinery to generate regulated movement of membrane organelles. 相似文献