title: A novel isoform of MAP4 organises the paraxial microtubule array required for muscle cell differentiation.
abstract: The microtubule cytoskeleton is critical for muscle cell differentiation and undergoes reorganisation into an array of paraxial microtubules, which serves as template for contractile sarcomere formation. In this study, we identify a previously uncharacterised isoform of microtubule-associated protein MAP4, oMAP4, as a microtubule organising factor that is crucial for myogenesis. We show that oMAP4 is expressed upon muscle cell differentiation and is the only MAP4 isoform essential for normal progression of the myogenic differentiation programme. Depletion of oMAP4 impairs cell elongation and cell-cell fusion. Most notably, oMAP4 is required for paraxial microtubule organisation in muscle cells and prevents dynein- and kinesin-driven microtubule-microtubule sliding. Purified oMAP4 aligns dynamic microtubules into antiparallel bundles that withstand motor forces in vitro. We propose a model in which the cooperation of dynein-mediated microtubule transport and oMAP4-mediated zippering of microtubules drives formation of a paraxial microtubule array that provides critical support for the polarisation and elongation of myotubes.
authors.affiliation: Centre for Mechanochemical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Binyam
authors.initials: B
authors.lastname: Mogessie
authors.affiliation: Centre for Mechanochemical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Roth
authors.affiliation: Centre for Mechanochemical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Rahil
authors.affiliation: Centre for Mechanochemical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Anne
authors.identifier: http://orcid.org/0000-0003-2067-9041
authors.initials: A
authors.lastname: Straube
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004398:Dyneins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D004398:Dyneins; D016547:Kinesins
keywords: cell biology; microtubule organisation; microtubule-associated proteins; molecular motors; mouse; none