The effect of motor-induced shaft dynamics on microtubule stability and length (original) (raw)
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How cellular membranes can regulate microtubule network
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology, 2010
Microtubule array in eukaryotic cells supports directed transport of various cargoes driven by motor proteins. The arrangement of microtubules in cytoplasm is not stochastic; they are organized in a cer tain way setting a system of coordinates for intracellular transport. Most cultured fibroblast like cells possess a radial microtubule array with the minus ends of microtubules gathered on the centrosome and plus ends directed towards the periphery of the cell. Mechanisms that regulate the formation of radial microtubule sys tem remain unclear. Usually centrosome works as a microtubule organizing center; however, the radial sys tem of microtubules can be formed without centrosome participation. At least in some cases microtubule net work can be organized by dynein-dynactin complexes associated with membrane vesicles. Membrane vesi cles can nucleate microtubules, anchor them and move along them. However, the role of membrane organelles in microtubule organization began to attract attention of researches only recently. It this review we summarize the data indicating that membrane organelles can organize microtubules, providing "tracks" for their subsequent transport.
Hither and yon: a review of bi-directional microtubule-based transport
2004
Active transport is critical for cellular organization and function, and impaired transport has been linked to diseases such as neuronal degeneration. Much long distance transport in cells uses opposite polarity molecular motors of the kinesin and dynein families to move cargos along microtubules. It is increasingly clear that many cargos are moved by both sets of motors, and frequently reverse course. This review compares this bi-directional transport to the more well studied uni-directional transport. It discusses some bi-directionally moving cargos, and critically evaluates three different physical models for how such transport might occur. It then considers the evidence for the number of active motors per cargo, and how the net or average direction of transport might be controlled. The likelihood of a complex linking the activities of kinesin and dynein is also discussed. The paper concludes by reviewing elements of apparent universality between different bi-directionally moving cargos and by briefly considering possible reasons for the existence of bi-directional transport.
Evidence for a Novel Affinity Mechanism of Motor-assisted Transport Along Microtubules
Molecular Biology of the Cell, 2000
In microtubule (MT) translocation assays, using colloidal gold particles coupled to monoclonal tubulin antibodies to mark positions along MTs, we found that relative motion is possible between the gold particle and an MT, gliding on dynein or kinesin. Such motion evidently occurred by an affinity release and rebinding mechanism that did not require motor activity on the particle. As the MTs moved, particles drifted to the trailing edge of the MT and then were released. Sometimes the particles transferred from one MT to another, moving orthogonally. Although motion of the particles was uniformly rearward, movement was toward the (Ϫ) or (ϩ) end of the MT, depending on whether dynein or kinesin, respectively, was used in the assay. These results open possibilities for physiological mechanisms of organelle and other movement that, although dependent on motor-driven microtubule transport, do not require direct motor attachment between the organelle and the microtubule. Our observations on the direction of particle drift and time of release may also provide confirmation in a dynamic system for the conclusion that  tubulin is exposed at the (ϩ) end of the MT.
Cytoskeleton, 2013
The spatial organization of the microtubule (MT) network directs cell polarity and mitosis. It is finely regulated by hundreds of different types of microtubule-associated proteins and molecular motors whose specific functions are difficult to investigate directly in cells. Here, we have investigated their functions using geometrically controlled MT networks in vitro in cellfree assay. This was achieved by developing a new method to spatially define MT nucleation using MT microseeds adsorbed on a micropatterned glass substrate. This method could be used to control MT growth and the induction of complex MT networks. We selected the interaction of two radial arrays of dynamic and polarized MTs to analyze the formation of the central antiparallel MT bundle. We investigated the effects of the MT cross-linker anaphase spindle elongation 1 (Ase1) and the kinesin motor Klp2, which are known to regulate MT organization in the spindle midzone. We thus identified the respective roles of each protein and revealed their synergy on the establishment of stable antiparallel MT bundles by quantifying MT interactions over hundreds of comparable MT networks. V C 2012 Wiley Periodicals, Inc
The role of microtubule movement in bidirectional organelle transport
Proceedings of the National Academy of Sciences, 2008
We study the role of microtubule movement in bidirectional organelle transport in Drosophila S2 cells and show that EGFPtagged peroxisomes in cells serve as sensitive probes of motor induced, noisy cytoskeletal motions. Multiple peroxisomes move in unison over large time windows and show correlations with microtubule tip positions, indicating rapid microtubule fluctuations in the longitudinal direction. We report the first high-resolution measurement of longitudinal microtubule fluctuations performed by tracing such pairs of co-moving peroxisomes. The resulting picture shows that motor-dependent longitudinal microtubule oscillations contribute significantly to cargo movement along microtubules. Thus, contrary to the conventional view, organelle transport cannot be described solely in terms of cargo movement along stationary microtubule tracks, but instead includes a strong contribution from the movement of the tracks. intracellular transport ͉ molecular motors ͉ kinesin ͉ dynein ͉ cytoskeleton M olecular motor-mediated transport along microtubules is an extensively studied phenomenon in vitro (1-3). Despite significant advances in vitro, understanding how intracellular transport works in vivo still remains one of the big challenges in cell biology. The question of how cellular cargos find their way through the cytoplasm and get targeted to their temporary or final destinations lies at the heart of the problem. One of the major puzzles in this context is the so-called bidirectional organelle transport. The majority of cargos in the cell move in a bidirectional and often remarkably symmetric manner (4, 5). Despite the known kinetic and dynamic asymmetry of the underlying plus-and minus-end directed microtubule motors, the vesicles seem to move with the same rates and run length distributions, and exhibit identical stalling forces, in each direction (4-7). Furthermore, inhibition of transport in one direction typically results in the inhibition of movement in the opposite direction as well (4-11).
Direct interaction of microtubule- and actin-based transport motors
Nature, 1999
The microtubule network is thought to be used for long-range transport of cellular components in animal cells whereas the actin network is proposed to be used for short-range transport, although the mechanism(s) by which this transport is coordinated is poorly understood. For example, in sea urchins long-range Ca2+-regulated transport of exocytotic vesicles requires a microtubule-based motor, whereas an actin-based motor is used for short-range transport. In neurons, microtubule-based kinesin motor proteins are used for long-range vesicular transport but microtubules do not extend into the neuronal termini, where actin filaments form the cytoskeletal framework, and kinesins are rapidly degraded upon their arrival in neuronal termini, indicating that vesicles may have to be transferred from microtubules to actin tracks to reach their final destination. Here we show that an actin-based vesicle-transport motor, MyoVA, can interact directly with a microtubule-based transport motor, KhcU...
Molecular Mechanism of Microtubules Dynamics and its Precise Regulation Inside Cells
Microtubules are tubulin polymers that use nucleoside triphosphate (GTP) hydrolysis for polymerization. Microtubules (MTs) are involved in diverse and dynamic cellular functions like cell shape maintenance, cell division, cell migration, and signalling. Microtubules display dynamic behaviour of Treadmilling and microtubule dynamics, these processes are precisely regulated by microtubule associated proteins. Inside the cells, soluble and polymeric fraction of tubulin is in equilibrium state that is regulated by microtubule polymerizing and depolymerizing proteins.
Regulation of cell migration by dynamic microtubules
Seminars in Cell & Developmental Biology, 2011
Microtubules define the architecture and internal organisation of cells by positioning organelles and activities, as well as by supporting cell shape and mechanics. One of the major functions of microtubules is the control of polarized cell motility. In order to support the asymmetry of polarized cells, microtubules have to be organised asymmetrically themselves. Asymmetry in microtubule distribution and stability is regulated by multiple molecular factors, most of which are microtubule-associated proteins that locally control microtubule nucleation and dynamics. At the same time, the dynamic state of microtubules is key to the regulatory mechanisms by which microtubules regulate cell polarity, modulate cell adhesion and control force-production by the actin cytoskeleton. Here, we propose that even small alterations in microtubule dynamics can influence cell migration via several different microtubule-dependent pathways. We discuss regulatory factors, potential feedback mechanisms due to functional microtubule-actin crosstalk and implications for cancer cell motility.
Nature Communications, 2019
Accurate chromosome segregation relies on microtubule end conversion, the ill-understood ability of kinetochores to transit from lateral microtubule attachment to durable association with dynamic microtubule plus-ends. The molecular requirements for this conversion and the underlying biophysical mechanisms are elusive. We reconstituted end conversion in vitro using two kinetochore components: the plus end–directed kinesin CENP-E and microtubule-binding Ndc80 complex, combined on the surface of a microbead. The primary role of CENP-E is to ensure close proximity between Ndc80 complexes and the microtubule plus-end, whereas Ndc80 complexes provide lasting microtubule association by diffusing on the microtubule wall near its tip. Together, these proteins mediate robust plus-end coupling during several rounds of microtubule dynamics, in the absence of any specialized tip-binding or regulatory proteins. Using a Brownian dynamics model, we show that end conversion is an emergent property ...
Microtubule dynamics: moving toward a multi-scale approach
Current Opinion in Cell Biology, 2018
Microtubule self-assembly dynamics serve to facilitate many vital cellular functions, such as chromosome segregation during mitosis and synaptic plasticity. However, the detailed atomistic basis of assembly dynamics has remained an unresolved puzzle. A key challenge is connecting together the vast range of relevant length-time scales, events happening at time scales ranging from nanoseconds, such as tubulin molecular interactions (Å-nm), to minutes-hours, such as the cellular response to microtubule dynamics during mitotic progression (μm). At the same time, microtubule interactions with associated proteins and binding agents, such as anti-cancer drugs, can strongly affect this dynamic process through atomic-level mechanisms that remain to be elucidated. New high-resolution technologies for investigating these interactions, including cryoelectron microscopy (EM) techniques and total internal reflection fluorescence (TIRF) microscopy, are yielding important new insights. Here, we focus on recent studies of microtubule dynamics, both theoretical and experimental, and how these findings shed new light on this complex phenomenon across length-time scales, from Å to μm and from nanoseconds to minutes.