Myosin VI Rewrites the Rules for Myosin Motors

Department of Physiology, University of Pennsylvania School of Medicine, B700 Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Cell (Impact Factor: 32.24). 05/2010; 141(4):573-82. DOI: 10.1016/j.cell.2010.04.028
Source: PubMed

ABSTRACT Myosin VI is the only type of myosin motor known to move toward the minus ends of actin filaments. This reversal in the direction of its movement is in part a consequence of the repositioning of its lever arm. In addition, myosin VI has a number of other specialized structural and functional adaptations that optimize performance of its unique cellular roles. Given that other classes of myosins may share some of these features, understanding the design principles of myosin VI will help guide the study of the functions of myosins that adopt similar strategies.

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Available from: Anne Houdusse, Sep 29, 2015
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    • "The C-terminal part of the tail forms a globular domain, which is essential for cargo binding through its interaction with binding partners (Sweeney and Houdusse, 2007, 2010; Chibalina et al., 2009; Karolczak et al., 2013; Tumbarello et al., 2013). The data gathered so far indicate that MVI acting as molecular motor and/or an anchor is engaged in endocytosis and intracellular transport of vesicles and organelles , cell migration, maintenance of the Golgi apparatus, actin cytoskeleton organization, autophagy and possibly in gene transcription (Vreugde et al., 2006; Sweeney and Houdusse, 2007, 2010; Chibalina et al., 2009; Majewski et al., 2011, 2012; Tumbarello et al., 2012, 2013). "
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    ABSTRACT: Myosin VI (MVI) is a unique unconventional myosin translocating, unlike other myosins, towards the minus end of actin filaments. It is involved in numerous cellular processes such as endocytosis, intracellular trafficking, cell migration, and transcription. In mammalian skeletal muscles it localizes mainly to sarcoplasmic reticulum and is also present within the muscle nuclei and at the neuromuscular junction (Karolczak et al. Histochem Cell Biol 2013; 23:219-228). We have also shown that in denervated rat hindlimb muscle the MVI expression level is significantly increased and its localization is changed, indicating an important role of MVI in striated muscle pathology. Here, we addressed this problem by examining the distribution and expression levels of myosin VI in biopsies of skeletal muscles from patients with different myopathies. We found that, particularly in myopathies associated with fiber atrophy, the amount of MVI was enhanced and its localization in affected fibers was changed. Also, since a mutation within the human MVI gene was shown to be associated with cardiomyopathy, we assessed MVI localization and expression level in cardiac muscle using wild type and MLP(−/−) mice, a dilated cardiomyopathy model. No significant difference in MVI expression level was observed for both types of animals. MVI was found at intercalated discs and also at the sarcoplasmic reticulum. In the knockout mice, it was also present in ring-like structures surrounding the nuclei. The data indicate that in striated muscle MVI could be engaged in sarcoplasmic reticulum maintenance and/or functioning, vesicular transport, signal transmission and possibly in gene transcription. Anat Rec, 297:1706–1713, 2014. © 2014 Wiley Periodicals, Inc.
    The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 09/2014; 297(9). DOI:10.1002/ar.22967 · 1.54 Impact Factor
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    • "The unusual lever arm design (including the unusual converter rearrangements; Mé né trey et al., 2007) that has evolved for myosin VI may be specialized for different functional properties as compared to a more conventional lever arm design, such as found in myosin Va. The myosin VI lever arm design could favor myosin VI remaining on the same actin filament when trafficking in a dense cellular actin network (Sweeney and Houdusse, 2010), allowing more efficient transport as well as load-dependent anchoring. There is in vitro evidence suggesting that myosin VI does not switch actin filaments as easily as myosin Va (Brawley and Rock, 2009; Ali et al., 2013). "
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    ABSTRACT: It is unclear whether the reverse-direction myosin (myosin VI) functions as a monomer or dimer in cells and how it generates large movements on actin. We deleted a stable, single-α-helix (SAH) domain that has been proposed to function as part of a lever arm to amplify movements without impact on in vitro movement or in vivo functions. A myosin VI construct that used this SAH domain as part of its lever arm was able to take large steps in vitro but did not rescue in vivo functions. It was necessary for myosin VI to internally dimerize, triggering unfolding of a three-helix bundle and calmodulin binding in order to step normally in vitro and rescue endocytosis and Golgi morphology in myosin VI-null fibroblasts. A model for myosin VI emerges in which cargo binding triggers dimerization and unfolds the three-helix bundle to create a lever arm essential for in vivo functions.
    Cell Reports 08/2014; 8(5). DOI:10.1016/j.celrep.2014.07.041 · 8.36 Impact Factor
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    • "Myosins from this class are involved in diverse processes such as cytokinesis, transcription regulation, and endocytosis (Roberts et al. 2004; Sweeney and Houdusse 2010). Our phylogeny shows that homologs of this class are present in metazoans , choanoflagellates, filastereans, Corallochytrium limacisporum, and apusozoans, but not in fungi or amoebozoans (fig. "
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    ABSTRACT: Myosins are key components of the eukaryotic cytoskeleton, providing motility for a broad diversity of cargoes. Therefore, understanding the origin and evolutionary history of myosin classes is crucial to address the evolution of eukaryote cell biology. Here, we revise the classification of myosins using an updated taxon sampling that includes newly or recently sequenced genomes and transcriptomes from key taxa. We performed a survey of eukaryotic genomes and phylogenetic analyses of the myosin gene family, reconstructing the myosin toolkit at different key nodes in the eukaryotic tree of life. We also identified the phylogenetic distribution of myosin diversity in terms of number of genes, associated protein domains and number of classes in each taxa. Our analyses show that new classes (i.e. paralogs) and domain architectures were continuously generated throughout eukaryote evolution, with a significant expansion of myosin abundance and domain architectural diversity at the stem of Holozoa, predating the origin of animal multicellularity. Indeed, single-celled holozoans have the most complex myosin complement among eukaryotes, with paralogs of most myosins previously considered animal-specific. We recover a dynamic evolutionary history, with several lineage-specific expansions (e.g. the 'myosin III-like' gene family diversification in choanoflagellates), convergence in protein domain architectures (e.g. fungal and animal chitin synthase myosins), and important secondary losses. Overall, our evolutionary scheme demonstrates that the ancestral eukaryote likely had a complex myosin repertoire that included six genes with different protein domain architectures. Finally, we provide an integrative and robust classification, useful for future genomic and functional studies on this crucial eukaryotic gene family.
    Genome Biology and Evolution 01/2014; DOI:10.1093/gbe/evu013 · 4.23 Impact Factor
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