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Disruption of KIF17–Mint1 interaction by CaMKII-dependent phosphorylation: a molecular model of kinesin–cargo release

Nature Cell Biology volume 10, pages 19–29 (2008)Cite this article

Abstract

Establishment and maintenance of cell structures and functions are highly dependent on the efficient regulation of intracellular transport in which proteins of the kinesin superfamily (KIFs) are very important. In this regard, how KIFs regulate the release of their cargo is a critical process that remains to be elucidated. To address this specific question, we have investigated the mechanism behind the regulation of the KIF17–Mint1 interaction. Here we report that the tail region of the molecular motor KIF17 is regulated by phosphorylation. Using direct visualization of protein–protein interaction by FRET and various in vitro and in vivo approaches we have demonstrated that CaMKII-dependent phosphorylation of KIF17 on Ser 1029 disrupts the KIF17–Mint1 association and results in the release of the transported cargo from its microtubule-based transport.

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Figure 1: Binding domains on KIF17 tail region and interaction with Mint1.
Figure 2: Disruption of KIF17–Mint1 interaction by CaMKII-dependent phosphorylation and FRET analysis of KIF17-Mint1 interaction using KIF17 phosphorylated peptides.
Figure 3: CaMKII interacts with KIF17.
Figure 4: Interaction and distribution of KIF17 and CaMKII in vivo.
Figure 5: CaMKII phosphorylates KIF17 on Ser 1029.
Figure 6: Phosphorylation of KIF17 by CaMKII in vivo and KIF17–Mint1 interaction.
Figure 7: FRET analysis of KIF17–Mint1 interaction using KIF17 mutated peptides.
Figure 8: Illustration of KIF17 unloading mechanism.

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Acknowledgements

We thank T. Meyer (Stanford University, CA) for the GFP–CaMKII constructs, Y. Okada (Hirokawa Laboratory) for helpful discussions and S. Hiromi (Hirokawa Laboratory) for the hippocampal neuron preparations. This work was supported by a grant-in-aid for specially-promoted research from the Japanese Ministry of Education, Culture, Sports, Science and Technology to N.H.

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  1. Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan

    Laurent Guillaud, Richard Wong & Nobutaka Hirokawa

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Correspondence to Nobutaka Hirokawa.

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Guillaud, L., Wong, R. & Hirokawa, N. Disruption of KIF17–Mint1 interaction by CaMKII-dependent phosphorylation: a molecular model of kinesin–cargo release. Nat Cell Biol 10, 19–29 (2008). https://doi.org/10.1038/ncb1665

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