Abstract
Oxysterol-binding protein (OSBP)-related protein 3 (ORP3) is highly
expressed in epithelial, neuronal and hematopoietic cells, as well as in
certain forms of cancer. We assessed the function of ORP3 in HEK293
cells and in human macrophages. We show that ORP3 interacts with R-Ras, a
small GTPase regulating cell adhesion, spreading and migration. Gene
silencing of ORP3 in HEK293 cells results in altered
organization of the actin cytoskeleton, impaired cell-cell adhesion,
enhanced cell spreading and an increase of β1 integrin activity–effects
similar to those of constitutively active R-Ras(38V). Overexpression of
ORP3 leads to formation of polarized cell-surface protrusions, impaired
cell spreading and decreased β1 integrin activity. In primary
macrophages, overexpression of ORP3 leads to the disappearance of
podosomal structures and decreased phagocytotic uptake of latex beads,
consistent with a role in actin regulation. ORP3 is phosphorylated when
cells lose adhesive contacts, suggesting that it is subject to
regulation by outside-in signals mediated by adhesion receptors. The
present findings demonstrate a new function of ORP3 as part of the
machinery that controls the actin cytoskeleton, cell polarity and cell
adhesion.
Original language | English |
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Pages (from-to) | 695-705 |
Journal | Journal of Cell Science |
Volume | 121 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2008 |
MoE publication type | A1 Journal article-refereed |
Keywords
- Actin cytoskeleton
- Cell adhesion
- Cell polarization
- Cell spreading
- HEK293
- Macrophages
- Oxysterol-binding protein
- R-Ras