Molecular Motors: Strategies to Get Along

Department of Developmental and Cell Biology, University of California Irvine, California 92697, USA.
Current Biology (Impact Factor: 9.57). 12/2004; 14(22):R971-82. DOI: 10.1016/j.cub.2004.10.046
Source: PubMed


The majority of active transport in the cell is driven by three classes of molecular motors: the kinesin and dynein families that move toward the plus-end and minus-end of microtubules, respectively, and the unconventional myosin motors that move along actin filaments. Each class of motor has different properties, but in the cell they often function together. In this review we summarize what is known about their single-molecule properties and the possibilities for regulation of such properties. In view of new results on cytoplasmic dynein, we attempt to rationalize how these different classes of motors might work together as part of the intracellular transport machinery. We propose that kinesin and myosin are robust and highly efficient transporters, but with somewhat limited room for regulation of function. Because cytoplasmic dynein is less efficient and robust, to achieve function comparable to the other motors it requires a number of accessory proteins as well as multiple dyneins functioning together. This necessity for additional factors, as well as dynein's inherent complexity, in principle allows for greatly increased control of function by taking the factors away either singly or in combination. Thus, dynein's contribution relative to the other motors can be dynamically tuned, allowing the motors to function together differently in a variety of situations.

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    • "The mitotic spindle, nucleated by MTOCs, is a bipolar array of microtubules (MTs) that provides the force required to segregate chromosomes. This mitotic spindle is synergistically modulated by motor proteins (Mallik and Gross, 2004), the plus end directed kinesins and the minus end directed dyneins, and MAPs which dynamically alter the rate of microtubule stability. The unequal rate of MT polymerization and depolymerization provides the push-pull forces that mediate pole-ward movement of segregated chromosomes into two daughter cells. "
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    ABSTRACT: High fidelity chromosome segregation during cell division depends on a series of concerted interdependent interactions. Using a systems biology approach, we built a robust minimal computational model to comprehend mitotic events in dividing budding yeasts of two major phyla: Ascomycetes and Basidiomycetes. This model accurately reproduces experimental observations related to spindle alignment, nuclear migration, and microtubule dynamics during cell division in these yeasts. The model converges to the conclusion that biased nucleation of cytoplasmic microtubules is essential for directional nuclear migration. Two distinct pathways, based on the population of cytoplasmic microtubules and cortical dyneins, differentiate nuclear migration and spindle orientation in these two phyla. In addition, the model accurately predicts the contribution of specific classes of microtubules in chromosome segregation. Thus we present a model that offers a wider applicability to simulate the effects of perturbation of an event on the concerted process of the mitotic cell division.
    Molecular biology of the cell 08/2015; DOI:10.1091/mbc.E15-04-0236 · 4.47 Impact Factor
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    • "Motor proteins provide the driving force behind most cytoplasmic transport of proteins and vesicles [15], and microtubules have been shown to serve as " railroad tracks " that guide their movement [16]. We previously demonstrated that TM4SF1 interacted with myosin-X (Myo10) [5], a motor protein that binds microtubules through a C-terminal MyTH4-FERM domain cassette [17] [18] [19]. "
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    ABSTRACT: Transmembrane-4 L-six family member-1 (TM4SF1) is a small plasma membrane-associated glycoprotein that is highly and selectively expressed on the plasma membranes of tumor cells, cultured endothelial cells, and, in vivo, on tumor-associated endothelium. Immunofluorescence microscopy also demonstrated TM4SF1 in cytoplasm and, tentatively, within nuclei. With monoclonal antibody 8G4, and the finer resolution afforded by immuno-nanogold transmission electron microscopy, we now demonstrate TM4SF1 in uncoated cytoplasmic vesicles, nuclear pores and nucleoplasm. Because of its prominent surface location on tumor cells and tumor-associated endothelium, TM4SF1 has potential as a dual therapeutic target using an antibody drug conjugate (ADC) approach. For ADC to be successful, antibodies reacting with cell surface antigens must be internalized for delivery of associated toxins to intracellular targets. We now report that 8G4 is efficiently taken up into cultured endothelial cells by uncoated vesicles in a dynamin-dependent, clathrin-independent manner. It is then transported along microtubules through the cytoplasm and passes through nuclear pores into the nucleus. These findings validate TM4SF1 as an attractive candidate for cancer therapy with antibody-bound toxins that have the capacity to react with either cytoplasmic or nuclear targets in tumor cells or tumor-associated vascular endothelium. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 08/2015; 465(3). DOI:10.1016/j.bbrc.2015.07.142 · 2.30 Impact Factor
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    • "In addition to other cellular functions, microtubules play a central role in intra-cellular transportation. Through binding and translocation along microtubules, motor proteins such as kinesin travel along microtubules, driving transport of cargos inside cells [29] [30] [31] [32]. There are mutual effects of motor proteins on microtubules , and vice versa. "
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    ABSTRACT: While there have been many single-molecule studies of kinesin-1, most have been done along microtubules purified from bovine or porcine brain, and relatively little is known about how variations in tubulin might alter motor function. Of particular interest is transport along microtubules polymerized from tubulin purified from MCF7 breast cancer cells, both because these cells are a heavily studied model system to help understand breast cancer, and also because the microtubules are already established to have interesting polymerization/stability differences from bovine tubulin, suggesting that perhaps transport along them is also different. Thus, we carried out paired experiments to allow direct comparison of in vitro kinesin-1 translocation along microtubules polymerized from either human breast cancer cells (MCF7) or microtubules from bovine brain. We found surprising differences: on MCF7 microtubules, kinesin-1's processivity is significantly reduced, although its velocity is only slightly altered.
    Biochemical and Biophysical Research Communications 10/2014; 454(4). DOI:10.1016/j.bbrc.2014.10.119 · 2.30 Impact Factor
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