The R-Ras interaction partner ORP3 regulates cell adhesion

Markku Lehto, Mikko I. Mäyränpää, Teijo Pellinen, Pekka Ihalmo, Sanna Lehtonen, Petri T. Kovanen, Per-Henrik Groop, Johanna Ivaska, Vesa M. Olkkonen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

46 Citations (Scopus)

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 languageEnglish
Pages (from-to)695 - 705
Number of pages11
JournalJournal of Cell Science
Volume121
Issue number5
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fingerprint

Cell Adhesion
Proteins
HEK293 Cells
Actin Cytoskeleton
Integrins
Cell Surface Extensions
Macrophages
Cell Polarity
Monomeric GTP-Binding Proteins
Gene Silencing
Microspheres
Adhesives
Cell Movement
Actins
Neoplasms

Keywords

  • Actin cytoskeleton
  • Cell adhesion
  • Cell polarization
  • Cell spreading
  • HEK293
  • Macrophages
  • Oxysterol-binding protein
  • R-Ras

Cite this

Lehto, M., Mäyränpää, M. I., Pellinen, T., Ihalmo, P., Lehtonen, S., Kovanen, P. T., ... Olkkonen, V. M. (2008). The R-Ras interaction partner ORP3 regulates cell adhesion. Journal of Cell Science, 121(5), 695 - 705. https://doi.org/10.1242/jcs.016964
Lehto, Markku ; Mäyränpää, Mikko I. ; Pellinen, Teijo ; Ihalmo, Pekka ; Lehtonen, Sanna ; Kovanen, Petri T. ; Groop, Per-Henrik ; Ivaska, Johanna ; Olkkonen, Vesa M. / The R-Ras interaction partner ORP3 regulates cell adhesion. In: Journal of Cell Science. 2008 ; Vol. 121, No. 5. pp. 695 - 705.
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Lehto, M, Mäyränpää, MI, Pellinen, T, Ihalmo, P, Lehtonen, S, Kovanen, PT, Groop, P-H, Ivaska, J & Olkkonen, VM 2008, 'The R-Ras interaction partner ORP3 regulates cell adhesion', Journal of Cell Science, vol. 121, no. 5, pp. 695 - 705. https://doi.org/10.1242/jcs.016964

The R-Ras interaction partner ORP3 regulates cell adhesion. / Lehto, Markku; Mäyränpää, Mikko I.; Pellinen, Teijo; Ihalmo, Pekka; Lehtonen, Sanna; Kovanen, Petri T.; Groop, Per-Henrik; Ivaska, Johanna; Olkkonen, Vesa M. (Corresponding Author).

In: Journal of Cell Science, Vol. 121, No. 5, 2008, p. 695 - 705.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - The R-Ras interaction partner ORP3 regulates cell adhesion

AU - Lehto, Markku

AU - Mäyränpää, Mikko I.

AU - Pellinen, Teijo

AU - Ihalmo, Pekka

AU - Lehtonen, Sanna

AU - Kovanen, Petri T.

AU - Groop, Per-Henrik

AU - Ivaska, Johanna

AU - Olkkonen, Vesa M.

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Actin cytoskeleton

KW - Cell adhesion

KW - Cell polarization

KW - Cell spreading

KW - HEK293

KW - Macrophages

KW - Oxysterol-binding protein

KW - R-Ras

U2 - 10.1242/jcs.016964

DO - 10.1242/jcs.016964

M3 - Article

VL - 121

SP - 695

EP - 705

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 5

ER -

Lehto M, Mäyränpää MI, Pellinen T, Ihalmo P, Lehtonen S, Kovanen PT et al. The R-Ras interaction partner ORP3 regulates cell adhesion. Journal of Cell Science. 2008;121(5):695 - 705. https://doi.org/10.1242/jcs.016964