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J Cell Biol. 2019 Apr 1;218(4):1298-1318. doi: 10.1083/jcb.201808065. Epub 2019 Feb 15.

MAP7 family proteins regulate kinesin-1 recruitment and activation.

Author information

1
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
2
Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland.
3
Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlands.
4
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences and The Netherlands Proteomics Centre, Utrecht University, Utrecht, Netherlands.
5
Biozentrum, University of Basel, Basel, Switzerland.
6
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands a.akhmanova@uu.nl.

Abstract

Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7 proteins. We found that all four mammalian MAP7 family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1, and MAP7D3 act redundantly to enable kinesin-1-dependent transport and microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions. In vitro, purified MAP7 and MAP7D3 increase microtubule landing rate and processivity of kinesin-1 through transient association with the motor. MAP7 proteins promote binding of kinesin-1 to microtubules both directly, through the N-terminal microtubule-binding domain and unstructured linker region, and indirectly, through an allosteric effect exerted by the kinesin-binding C-terminal domain. Compared with MAP7, MAP7D3 has a higher affinity for kinesin-1 and a lower affinity for microtubules and, unlike MAP7, can be cotransported with the motor. We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules.

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