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PMID: 18158328 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 179 ·No. 7 ·2007-12-31 ·Pages 1569-82

Pi X, Ren R, Kelley R, Zhang C, Moser M, Bohil AB, Divito M, Cheney RE, Patterson C

Abstract

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.

MeSH Terms
Animals Bone Morphogenetic Protein 6 Bone Morphogenetic Protein Receptors/agonists,metabolism Bone Morphogenetic Protein Receptors, Type I/metabolism Bone Morphogenetic Proteins/genetics,metabolism Cell Differentiation/physiology Cell Movement/physiology Cell Polarity/physiology Cells, Cultured Endothelial Cells/metabolism,ultrastructure Gene Expression Regulation, Developmental/genetics Mice Myosins/metabolism Neovascularization, Physiologic/physiology Pseudopodia/metabolism,ultrastructure Signal Transduction/physiology Smad Proteins/metabolism
Chemicals
Bmp6 protein, mouse Bone Morphogenetic Protein 6 Bone Morphogenetic Proteins Myo10 protein, mouse Smad Proteins Bmpr1b protein, mouse Bone Morphogenetic Protein Receptors Bone Morphogenetic Protein Receptors, Type I Myosins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Pi Xinchun
Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Ren Rongqin
Kelley Russell
Zhang Chunlian
Moser Martin
Bohil Aparna B
Divito Melinda
Cheney Richard E
Patterson Cam
References (31)
31 references, click to expand
  1. A new direct-viewing chemotaxis chamber.
    J Cell Sci. 1991 Aug;99 ( Pt 4):769-75 PMID: 1770004
  2. The actin cytoskeleton.
    Electron Microsc Rev. 1988;1(1):155-74 PMID: 2485000
  3. Bone morphogenetic proteins in development.
    Curr Opin Genet Dev. 1996 Aug;6(4):432-8 PMID: 8791534
  4. The molecular biology of axon guidance.
    Science. 1996 Nov 15;274(5290):1123-33 PMID: 8895455
  5. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development.
    Development. 1996 Oct;122(10):2977-86 PMID: 8898212
  6. Growth/differentiation factor-5 induces angiogenesis in vivo.
    Exp Cell Res. 1997 Aug 25;235(1):218-26 PMID: 9281371
  7. TGF-beta signal transduction.
    Annu Rev Biochem. 1998;67:753-91 PMID: 9759503
  8. Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5.
    Development. 1999 Apr;126(8):1571-80 PMID: 10079220
  9. [Effect of colchicine on remote phases of growing capillaries in the brain].
    Arkh Patol. 1963;35(3):38-44 PMID: 14033622
  10. BMK1/ERK5 is a novel regulator of angiogenesis by destabilizing hypoxia inducible factor 1alpha.
    Circ Res. 2005 Jun 10;96(11):1145-51 PMID: 15879308
  11. Dependence of Drosophila wing imaginal disc cytonemes on Decapentaplegic.
    Nature. 2005 Sep 22;437(7058):560-3 PMID: 16177792
  12. Myosin-X: a molecular motor at the cell's fingertips.
    Trends Cell Biol. 2005 Oct;15(10):533-9 PMID: 16140532
  13. Bone morphogenetic protein 2 (BMP-2) and induction of tumor angiogenesis.
    J Cancer Res Clin Oncol. 2005 Nov;131(11):741-50 PMID: 16136355
  14. Myo10 in brain: developmental regulation, identification of a headless isoform and dynamics in neurons.
    J Cell Sci. 2006 Jan 1;119(Pt 1):184-94 PMID: 16371656
  15. Myosin-X is a molecular motor that functions in filopodia formation.
    Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12411-6 PMID: 16894163
  16. Gene expression profiles identify a role for cyclooxygenase 2-dependent prostanoid generation in BMP6-induced angiogenic responses.
    Blood. 2007 Apr 1;109(7):2847-53 PMID: 17119124
  17. Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis.
    Microvasc Res. 1996 Mar;51(2):260-72 PMID: 8778579
  18. Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling.
    J Neurooncol. 2000 Oct-Nov;50(1-2):1-15 PMID: 11245270
  19. Exogenously regulated stem cell-mediated gene therapy for bone regeneration.
    Mol Ther. 2001 Apr;3(4):449-61 PMID: 11319905
  20. Myosin-X is an unconventional myosin that undergoes intrafilopodial motility.
    Nat Cell Biol. 2002 Mar;4(3):246-50 PMID: 11854753
  21. Bone morphogenetic proteins stimulate angiogenesis through osteoblast-derived vascular endothelial growth factor A.
    Endocrinology. 2002 Apr;143(4):1545-53 PMID: 11897714
  22. Overview of bone morphogenetic proteins.
    Spine (Phila Pa 1976). 2002 Aug 15;27(16 Suppl 1):S2-8 PMID: 12205411
  23. Stimulation of Id1 expression by bone morphogenetic protein is sufficient and necessary for bone morphogenetic protein-induced activation of endothelial cells.
    Circulation. 2002 Oct 22;106(17):2263-70 PMID: 12390958
  24. BMP receptor 1b is required for axon guidance and cell survival in the developing retina.
    Dev Biol. 2003 Apr 1;256(1):34-48 PMID: 12654290
  25. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia.
    J Cell Biol. 2003 Jun 23;161(6):1163-77 PMID: 12810700
  26. Controlling cell fate by bone morphogenetic protein receptors.
    Mol Cell Endocrinol. 2003 Dec 15;211(1-2):105-13 PMID: 14656483
  27. Myosin-X provides a motor-based link between integrins and the cytoskeleton.
    Nat Cell Biol. 2004 Jun;6(6):523-31 PMID: 15156152
  28. The formation of capillary basement membranes during internal vascularization of the rat's cerebral cortex.
    Z Zellforsch Mikrosk Anat. 1972;133(2):231-48 PMID: 5082884
  29. Early vascularization of the embryonic cerebral cortex: Golgi and electron microscopic studies.
    J Comp Neurol. 1985 Nov 8;241(2):237-49 PMID: 4067017
  30. Vascular physiology. A family of angiogenic peptides.
    Nature. 1987 Oct 22-28;329(6141):671-2 PMID: 2444887
  31. Regulators of angiogenesis.
    Annu Rev Physiol. 1991;53:217-39 PMID: 1710435
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200704010
Published
2007-12-31
Epub
2007-00-24
Pages
1569-82
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2373493
Subset
IM
Grants
NHLBI NIH HHS · HL080166 · United States
NHLBI NIH HHS · R01 HL061656 · United States
NHLBI NIH HHS · R01 HL072347 · United States
NHLBI NIH HHS · HL 072347 · United States
NHLBI NIH HHS · HL 61656 · United States
NHLBI NIH HHS · HL 03658 · United States
NHLBI NIH HHS · P01 HL080166 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1083/jcb.200704010 PMC Full Text View journal details
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