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Mechanisms of Kinesin-1 activation by Ensconsin/MAP7 in vivo

Mathieu Métivier, Brigette Y. Monroy, Emmanuel Gallaud, Renaud Caous, Aude Pascal, Laurent Richard-Parpaillon, Antoine Guichet, Kassandra M. Ori-McKenney, Régis Giet
doi: https://doi.org/10.1101/325035
Mathieu Métivier
1University of Rennes, CNRS, IGDR (Institute of Genetics and Development of Rennes) - UMR 6290, F-35000 Rennes, France
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Brigette Y. Monroy
3University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
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Emmanuel Gallaud
1University of Rennes, CNRS, IGDR (Institute of Genetics and Development of Rennes) - UMR 6290, F-35000 Rennes, France
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Renaud Caous
1University of Rennes, CNRS, IGDR (Institute of Genetics and Development of Rennes) - UMR 6290, F-35000 Rennes, France
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Aude Pascal
1University of Rennes, CNRS, IGDR (Institute of Genetics and Development of Rennes) - UMR 6290, F-35000 Rennes, France
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Laurent Richard-Parpaillon
1University of Rennes, CNRS, IGDR (Institute of Genetics and Development of Rennes) - UMR 6290, F-35000 Rennes, France
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Antoine Guichet
2Institut Jacques Monod-Université Paris Diderot-Paris 7, 15 rue Hélène Brion, 75205 Paris cedex 13, France
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Kassandra M. Ori-McKenney
3University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
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Régis Giet
1University of Rennes, CNRS, IGDR (Institute of Genetics and Development of Rennes) - UMR 6290, F-35000 Rennes, France
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  • For correspondence: regis.giet@univ-rennes1.fr
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Abstract

Centrosome separation in Drosophila larval neuroblasts and asymmetric transport of embryonic determinants in oocytes are both microtubule-dependent processes that require Kinesin-1 activation by Ensconsin/microtubule-associated protein 7 (MAP7). However, the molecular mechanism used by Ensconsin to activate Kinesin-1 remains elusive. Ensconsin/ MAP7 contains an N-terminal microtubule-binding domain (MBD) and a C-terminal Kinesin-binding domain (KBD). Using rescue experiments in live flies, we show that KBD expression alone is sufficient to fully rescue Ensconsin-dependent centrosome separation defects, but not the fast oocyte streaming and the localization patterns of Staufen and Gurken proteins. Interestingly, we show here for the first time that KBD binds and stimulates Kinesin-1 binding to Mts in vivo and in vitro. We propose that the KBD/Kinesin-1 motor represents a minimal activation module that stimulates Kinesin-1 binding to Mts. Addition of the MBD, present in the full length Ensconsin allows this activation to occur directly on the Mt. Our data also suggest that in a very large cell with a complex microtubule network, but not in smaller cells, this dual activation by Ensconsin is essential for optimal Kinesin-1 targeting to the microtubule cytoskeleton.

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Posted July 27, 2018.
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Mechanisms of Kinesin-1 activation by Ensconsin/MAP7 in vivo
Mathieu Métivier, Brigette Y. Monroy, Emmanuel Gallaud, Renaud Caous, Aude Pascal, Laurent Richard-Parpaillon, Antoine Guichet, Kassandra M. Ori-McKenney, Régis Giet
bioRxiv 325035; doi: https://doi.org/10.1101/325035
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Mechanisms of Kinesin-1 activation by Ensconsin/MAP7 in vivo
Mathieu Métivier, Brigette Y. Monroy, Emmanuel Gallaud, Renaud Caous, Aude Pascal, Laurent Richard-Parpaillon, Antoine Guichet, Kassandra M. Ori-McKenney, Régis Giet
bioRxiv 325035; doi: https://doi.org/10.1101/325035

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