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Netrin-4 activates endothelial integrin {alpha}6{beta}1.
- Source :
-
Circulation research [Circ Res] 2011 Sep 16; Vol. 109 (7), pp. 770-4. Date of Electronic Publication: 2011 Jul 28. - Publication Year :
- 2011
-
Abstract
- Rationale: Netrin-4 regulates vascular development. Identity of netrin-4 endothelial receptor and its subsequent cell functions is controversial. We previously demonstrated that the inhibition of netrin-1 canonical receptors, Unc5B and neogenin, expressed by lymphatic endothelial cells, do not suppress netrin-4-induced cell signaling and functions. Netrin family members were shown to signal through a range of receptors, including integrins (such as α3β1, α6β1, and α6β4) in nonendothelial cells.<br />Objective: We tested whether integrins are netrin-4 receptors in the endothelium.<br />Methods and Results: The α6β1 integrin is expressed by endothelial cells, and binds netrin-4 in a dose-dependent manner. Inhibition of α6 or β1 integrin subunits suppresses netrin-4-induced endothelial cell migration, adhesion, and focal adhesion contact. Netrin-4-stimulated phosphorylation of Src kinase family, effectors of endothelial cell migration, is also abolished by α6 or β1 inhibition. Finally, netrin-4 and α6β1 integrin expression colocalize in mouse embryonic, intestine, and tumor vasculature.<br />Conclusions: The α6β1 integrin is a netrin-4 receptor in lymphatic endothelium and consequently represents a potential target to inhibit netrin-4-induced metastatic dissemination.
- Subjects :
- Animals
Blood Vessels embryology
Blood Vessels metabolism
Breast Neoplasms blood supply
Cell Adhesion
Cell Line, Tumor
Cell Movement
Female
Focal Adhesions metabolism
Humans
Integrin alpha6beta1 genetics
Intestines blood supply
Lymphatic Vessels metabolism
Mice
Netrins
Phosphorylation
Protein Binding
RNA Interference
Recombinant Proteins metabolism
Transfection
src-Family Kinases metabolism
Endothelial Cells metabolism
Integrin alpha6beta1 metabolism
Nerve Growth Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 109
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 21799154
- Full Text :
- https://doi.org/10.1161/CIRCRESAHA.111.247239