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Myosin-X provides a motor-based link between integrins and the cytoskeleton

Nature Cell Biology volume 6, pages 523–531 (2004)Cite this article

Abstract

Unconventional myosins are actin-based motors with a growing number of attributed functions1. Interestingly, it has been proposed that integrins are transported by unidentified myosins to facilitate cellular remodelling2. Here we present an interaction between the unconventional myosin-X (Myo10) FERM (band 4.1/ezrin/radixin/moesin) domain and an NPXY motif within β-integrin cytoplasmic domains. Importantly, knock-down of Myo10 by short interfering RNA impaired integrin function in cell adhesion, whereas overexpression of Myo10 stimulated the formation and elongation of filopodia in an integrin-dependent manner and relocalized integrins together with Myo10 to the tips of filopodia. This integrin relocalization and filopodia elongation did not occur with Myo10 mutants deficient in integrin binding or with a β1-integrin point mutant deficient in Myo10 binding. Taken together, these results indicate that Myo10-mediated relocalization of integrins might serve to form adhesive structures and thereby promote filopodial extension.

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Figure 1: Myo10 interacts with integrin β-subunit cytoplasmic domains.
Figure 2: Lobes F2 and F3 of Myo10-FERM domain interact with a conserved NPXY motif of integrin cytoplasmic tails.
Figure 3: Myo10 affects integrin-mediated cell adhesion and stimulates filopodia formation in an integrin-dependent manner.
Figure 4: Myo10 localizes integrins into filopodia dependent on the Myo10 to integrin interaction.
Figure 5: Myo10-mediated filopodia elongation requires the integrin-binding FERM regions of Myo10 and the Myo10-binding capacity of integrins.

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Acknowledgements

We thank E. Ruoslahti for providing the integrin β1 and β5 cDNA, K. M. Yamada and R. Pankov for providing GD25, GD25-β1-wt and GD25-β1-W775A cells, R. Agami for the pSuper vector, and A. Hofman, E.-K. Viklund and P. Lennartsson for technical assistance. We also thank the Center for Infectious Medicine for use of their confocal microscope supported by the Swedish Strategic Foundation. This study was supported by grants to S.S. from the Swedish Cancer Society and the Swedish Research Council, to H.Z. from the Swedish Society of Medicine and to R.E.C. from NIH (no. DC03299). H.Z. was supported by the Wenner-Gren Foundation in Sweden. S.S. holds a senior scientist position from the Swedish Research Council.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Division of Pathology F46, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, SE-141 86, Sweden

    Hongquan Zhang, Zhilun Li, Yunling Wang, Pernilla Lång & Staffan Strömblad

  2. Department of Gastroenterology and Institute of Gastroenterology, Nanfang Hospital, the First Military Medical University, Guangzhou, 510515, P.R. China

    Hongquan Zhang

  3. Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, 27599, NC, USA

    Jonathan S. Berg, Aurea D. Sousa, Aparna Bhaskar & Richard E. Cheney

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Zhang, H., Berg, J., Li, Z. et al. Myosin-X provides a motor-based link between integrins and the cytoskeleton. Nat Cell Biol 6, 523–531 (2004). https://doi.org/10.1038/ncb1136

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