Q1: Using information contained in the introduction of the paper and elsewhere,
ID: 80416 • Letter: Q
Question
Q1: Using information contained in the introduction of the paper and elsewhere, explain what factors determined the classification of Myo18B as an “unconventional” myosin (5pts)?
*Note: Please avoid copy paste , and write on your own words, and include sources if used
A Zebrafish Model for a Human Myopathy Associated with Mutation of the Unconventional Myosin MY018B Ritika Gurung, Yosuke Ono, Sarah Baxendale Samantha Lin Chiou Lee, Steven Moore Meredith Calvert, and Philip W. Ingham .,E2 A STAR Institute of Molecular and Cell Biology, Singapore 138673, Singapore, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore, The Living Systems Institute, University of Exeter, EX4 4QD UK, Department of Biomedical Science, University of Sheffield S10 2TN, UK, and Temasek Lifesciences Laboratory, Singapore 7604, Singapore ORCID ID: 0000-0001-8224-9958 (P.W.I ABSTRACT Myosin 18B is an unconventional myosin that has been mplicated in tumor progressio n in humans. In addition, loss-of function mutations of the MY018B gene have recently been identified in several patients exhibiting symptoms of nemaline myopathy n mouse, mutation of Myo18B results i early developmental arrest associated with cardiomyopathy, precluding analysis of its effects on skeletal muscle development. The zebrafish, frozen (fro) mutant was identified as one of a group of immotile mutants in the oss of birefringency in their skeletal muscle indicative of disrupted 996 Tubingen genetic screen. Mutant embryos display a sarcomeric organization. Using meiotic mapping, we localized the fro locus to the previous unannotated zebrafish myo18b gene the product of which shares close to 50% identity with its hum an ortholog. Transcription of myo 18b is restricted to fast-twitch the zebrafish embryo; consistent with this, fro mutant embryos exhibit defects specifically in their fast-twitch skeleta myocytes in muscles. We show that sarcomeric assembly is blocked rly stage in fro mu leading to the disorganized accumulation of tants, at an ea actin, myosin, and a-actini nd a complete loss of fibrillar organization in fast-twitch muscles KEYWORDS MY018B; nemaline myopathy, fast-twitch muscle; frozen. zebrafish YOSINS comprise a superfamily of actin driven motor ll muscle myosins as well as nonmuscle myosins (belonging proteins; although primarily known for their involve to Class II that resemble them in their ability to associate nto ment in muscle contraction, many additional functions have filaments; and unconventional, which refers to all other my been attributed to them, ranging from cell adhesion and osins. Among the latter type, members of six classes have polarity (reviewed by Vicente-Manzanares et al. 2009) to in been found to be expressed in muscle (Redowicz 2007) tracellular vesicular trafficking (reviewed by Akhmanova and The unconventional myosin MYO18B is encoded by a gene Hammer 2010) and transcription (Philimonenko et al. 2004 originally identified by sequence annotation of human chro ence comparisons of their Vreugde et al. 2006). Based on sequ mosome 22 and shown to share n 40% sequence identity with conserved motor domain, the eukaryotic myosins have been the previously described MY018A gene (Berg et al. 2001) signed to n 35 phylogenetic classes (Odronitz and Kollma Subsequent human genetic studies identified MYO 18B as a 2007; Heissler and Sellers 2016). Two different types of tumor suppressor gene, based on its deletion in a lung carci myosin can be distinguished: conventional, which refers to noma cell line and in 60% of all lung cancers assayed. (Nishioka et al. 2002). In an independent study, MY018B Copyright 2017 by the Genetics Society of America was identified in a human skeletal muscle complementary doi 0.1534 genetics. 116.19286A DNA (cDNA) library and found to be expressed in human Manuscript received June 20, 2016; accepted for publicat ovember 18, 2016 ion published Early Online November 21, 2016 cardiac muscle and testes, as well as in skeletal muscle Supplemental material is available online at www.genetics.org/ookup/suppldoi 10 (Nishioka et al. 2002, Salamon et al. 20030. Analyses of 534 genetics 6.19286 AV/DC Myo18B expression in the mouse are consistent with a role in These authors contributed equally to this work.0002 Corresponding author Lee Kong Chian School of Medicine, Nanyang Techn the development and maintenance of both cardiac and skeletal University. 50 Nanyang Ave. Singapore 639798, Singapore. E-mail: pingham muscle. A Myol8B:Lacz reporter gene is expressed in both the ntu.edu.sg Genetics, Vol. 05, 725-735 February 2017 725Explanation / Answer
Myo18B is an “unconventional” myosin as it is expressed mainly in:
Further, this gene appears to be a tumor suppressor gene and its downregulation leads to the development of cancer like in the case of the lung.
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