The myosin superfamily at a glance

Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Journal of Cell Science (Impact Factor: 5.43). 04/2012; 125(Pt 7):1627-32. DOI: 10.1242/jcs.094300
Source: PubMed
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    • "Myosin VI is an ATP hydrolysis coupled motor protein involved in many cellular functions including endocytosis, protein secretion and the maintenance of both the Golgi morphology and stereocilia [1]. It is a unique myosin in that it moves to the minus end of an actin filament [2], while all other myosins move to the plus end [3]. Recently, we proposed that myosin VI moves using three types of steps: large and small forward steps (minus end directed), and backward steps (plus end directed) [4] [5] [6]. "
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    ABSTRACT: Myosin VI is a processive myosin that has a unique stepping motion, which includes three kinds of steps: a large forward step, a small forward step and a backward step. Recently, we proposed the parallel lever arms model to explain the adjacent binding state, which is necessary for the unique motion. In this model, both lever arms are directed the same direction. However, experimental evidence has not refuted the possibility that the adjacent binding state emerges from myosin VI folding its lever arm extension (LAE). To clarify this issue, we constructed a myosin VI/V chimera that replaces the myosin VI LAE with the IQ3-6 domains of the myosin V lever arm, which cannot fold, and performed single molecule imaging. Our chimera showed the same stepping patterns as myosin VI, indicating the LAE is not responsible for the adjacent binding state.
    BIOPHYSICS 01/2015; 11. DOI:10.2142/biophysics.11.47
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    • "Myosin Superfamily M yosins are actin-dependent molecular motors that utilize the energy of ATP hydrolysis to generate force. The many functions of myosins include cell contractility, cell signaling, endocytosis, vesicle trafficking and protein/ RNA localization [Krendel and Mooseker, 2005; Woolner and Bement, 2009; Hartman and Spudich, 2012]. All myosins share certain structural and functional features, particularly the presence of an actin-binding head domain, which is also responsible for myosin ATPase activity. "
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    ABSTRACT: The actin cytoskeleton, which regulates cell polarity, adhesion, and migration, can influence cancer progression, including initial acquisition of malignant properties by normal cells, invasion of adjacent tissues, and metastasis to distant sites. Actin-dependent molecular motors, myosins, play key roles in regulating tumor progression and metastasis. In this review, we examine how non-muscle myosins regulate neoplastic transformation and cancer cell migration and invasion. Members of the myosin superfamily can act as either enhancers or suppressors of tumor progression. This review summarizes the current state of knowledge on how mutations or epigenetic changes in myosin genes and changes in myosin expression may affect tumor progression and patient outcomes and discusses the proposed mechanisms linking myosin inactivation or upregulation to malignant phenotype, cancer cell migration, and metastasis. © 2014 Wiley Periodicals, Inc.
    Cytoskeleton 08/2014; 71(8). DOI:10.1002/cm.21187 · 3.12 Impact Factor
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    • "Myosins participate in a variety of cellular processes, including cytokinesis , organellar transport, cell polarization, transcriptional regulation, intracellular transport, and signal transduction (Hofmann et al. 2009; Bloemink and Geeves 2011; Hartman et al. 2011). They bind to filamentous actin and produce physical forces by hydrolyzing ATP and converting chemical energy into mechanical force (Hartman and Spudich 2012). Both activities reside in the myosin head domain (PF00063). "
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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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