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A correction to this article has been published: Pi et al., J. Cell Biol. 184 (4) 611
Published online
doi:10.1083/jcb.200704010
The Journal of Cell Biology, Vol. 179, No. 7, 1569-1582
The Rockefeller University Press, 0021-9525 $30.00
© Pi et al.
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Article

Sequential roles for myosin-X in BMP6-dependent filopodial extension, migration, and activation of BMP receptors



Xinchun Pi1, Rongqin Ren1, Russell Kelley1, Chunlian Zhang1, Martin Moser4, Aparna B. Bohil2, Melinda DiVito2, Richard E. Cheney1,2, and Cam Patterson1,3

1 Carolina Cardiovascular Biology Center, 2 Department of Cell and Molecular Physiology, and 3 Department of Medicine, University of North Carolina, Chapel Hill, NC 27599
4 Innere Medizin III, Universität Freiburg, 79106 Freiburg, Germany

Correspondence to Cam Patterson: cpatters{at}med.unc.edu

Endothelial cell migration is an important step during angiogenesis, and its dysregulation contributes to aberrant neovascularization. The bone morphogenetic proteins (BMPs) are potent stimulators of cell migration and angiogenesis. Using microarray analyses, we find that myosin-X (Myo10) is a BMP target gene. In endothelial cells, BMP6-induced Myo10 localizes in filopodia, and BMP-dependent filopodial assembly decreases when Myo10 expression is reduced. Likewise, cellular alignment and directional migration induced by BMP6 are Myo10 dependent. Surprisingly, we find that Myo10 and BMP6 receptor ALK6 colocalize in a BMP6-dependent fashion. ALK6 translocates into filopodia after BMP6 stimulation, and both ALK6 and Myo10 possess intrafilopodial motility. Additionally, Myo10 is required for BMP6-dependent Smad activation, indicating that in addition to its function in filopodial assembly, Myo10 also participates in a requisite amplification loop for BMP signaling. Our data indicate that Myo10 is required to guide endothelial migration toward BMP6 gradients via the regulation of filopodial function and amplification of BMP signals.

Abbreviations used in this paper: BMP, bone morphogenetic protein; MEC, mouse intraembryonic endothelial cell; SEM, scanning EM.


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