Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles
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...
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doaj-b43640e9c1204849bad421793731c53f2020-11-24T21:27:43ZengElsevierCell Reports2211-12472014-09-01851522153210.1016/j.celrep.2014.07.041Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular RolesMonalisa Mukherjea0M. Yusuf Ali1Carlos Kikuti2Daniel Safer3Zhaohui Yang4Helena Sirkia5Virginie Ropars6Anne Houdusse7David M. Warshaw8H. Lee Sweeney9Department of Physiology, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, 700 CRB, Philadelphia, PA 19104-6085, USADepartment of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USAStructural Motility, Centre de Recherche, Institut Curie, 75248 Paris, FranceDepartment of Physiology, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, 700 CRB, Philadelphia, PA 19104-6085, USADepartment of Physiology, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, 700 CRB, Philadelphia, PA 19104-6085, USAStructural Motility, Centre de Recherche, Institut Curie, 75248 Paris, FranceStructural Motility, Centre de Recherche, Institut Curie, 75248 Paris, FranceStructural Motility, Centre de Recherche, Institut Curie, 75248 Paris, FranceDepartment of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USADepartment of Physiology, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, 700 CRB, Philadelphia, PA 19104-6085, USA 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. http://www.sciencedirect.com/science/article/pii/S2211124714006251 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Monalisa Mukherjea M. Yusuf Ali Carlos Kikuti Daniel Safer Zhaohui Yang Helena Sirkia Virginie Ropars Anne Houdusse David M. Warshaw H. Lee Sweeney |
spellingShingle |
Monalisa Mukherjea M. Yusuf Ali Carlos Kikuti Daniel Safer Zhaohui Yang Helena Sirkia Virginie Ropars Anne Houdusse David M. Warshaw H. Lee Sweeney Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles Cell Reports |
author_facet |
Monalisa Mukherjea M. Yusuf Ali Carlos Kikuti Daniel Safer Zhaohui Yang Helena Sirkia Virginie Ropars Anne Houdusse David M. Warshaw H. Lee Sweeney |
author_sort |
Monalisa Mukherjea |
title |
Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles |
title_short |
Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles |
title_full |
Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles |
title_fullStr |
Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles |
title_full_unstemmed |
Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles |
title_sort |
myosin vi must dimerize and deploy its unusual lever arm in order to perform its cellular roles |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2014-09-01 |
description |
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.
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url |
http://www.sciencedirect.com/science/article/pii/S2211124714006251 |
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