Two functional active conformations of the integrin α2β1, depending on activation condition and cell type

Gerlinde R. Van De Walle, Karen Vanhoorelbeke, Zs. Majer, Eszter Illyés, Johan Baert, Inge Pareyn, Hans Deckmyn

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

For several integrins, the existence of multiple conformational states has been studied intensively. For the integrin α2β1, a major collagen receptor on platelets and other cell types, however, no such experimental data were available thus far. Recently, our group has developed a monoclonal antibody IAC-1 sensitive to the molecular conformation of α2β1 because it only binds to the activated state of α2β1 on platelets, induced upon inside-out signaling. By investigating IAC-1 binding in combination with collagen binding after inside-out stimulation and outside manipulation, we demonstrated the existence of three different conformations of α2β1 on platelets and Chinese hamster ovary cells as follows: (i) a nonactivated, resting state with no collagen nor IAC-1 binding; (ii) an intermediate state, induced by outside manipulation, with collagen but no IAC-1 binding; and (iii) a fully activated state, induced after inside-out stimulation, with both collagen and IAC-1 binding. Moreover, these different conformational states of α2β1 are dependent on the cell type where α2β1 is expressed, as IAC-1 binding to peripheral blood mononuclear cells and Jurkat cells could also be induced by outside manipulation, in contrast to platelets and α2β1-expressing Chinese hamster ovary cells. Finally, we revealed a functional relevance for these different conformational states because the conformation of α2β1, induced after outside manipulation, resulted in significantly more cell spreading on coated collagen compared with nonactivated or inside-out stimulated cells.

Original languageEnglish
Pages (from-to)36873-36882
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number44
DOIs
Publication statusPublished - Nov 4 2005

Fingerprint

Integrins
Conformations
Platelets
Collagen
Chemical activation
Blood Platelets
Cricetulus
Cells
Collagen Receptors
Ovary
Molecular Conformation
Jurkat Cells
Blood
Monoclonal Antibodies
Blood Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Two functional active conformations of the integrin α2β1, depending on activation condition and cell type. / Van De Walle, Gerlinde R.; Vanhoorelbeke, Karen; Majer, Zs.; Illyés, Eszter; Baert, Johan; Pareyn, Inge; Deckmyn, Hans.

In: Journal of Biological Chemistry, Vol. 280, No. 44, 04.11.2005, p. 36873-36882.

Research output: Contribution to journalArticle

Van De Walle, GR, Vanhoorelbeke, K, Majer, Z, Illyés, E, Baert, J, Pareyn, I & Deckmyn, H 2005, 'Two functional active conformations of the integrin α2β1, depending on activation condition and cell type', Journal of Biological Chemistry, vol. 280, no. 44, pp. 36873-36882. https://doi.org/10.1074/jbc.M508148200
Van De Walle, Gerlinde R. ; Vanhoorelbeke, Karen ; Majer, Zs. ; Illyés, Eszter ; Baert, Johan ; Pareyn, Inge ; Deckmyn, Hans. / Two functional active conformations of the integrin α2β1, depending on activation condition and cell type. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 44. pp. 36873-36882.
@article{061c092145464e93867a60484880f4b7,
title = "Two functional active conformations of the integrin α2β1, depending on activation condition and cell type",
abstract = "For several integrins, the existence of multiple conformational states has been studied intensively. For the integrin α2β1, a major collagen receptor on platelets and other cell types, however, no such experimental data were available thus far. Recently, our group has developed a monoclonal antibody IAC-1 sensitive to the molecular conformation of α2β1 because it only binds to the activated state of α2β1 on platelets, induced upon inside-out signaling. By investigating IAC-1 binding in combination with collagen binding after inside-out stimulation and outside manipulation, we demonstrated the existence of three different conformations of α2β1 on platelets and Chinese hamster ovary cells as follows: (i) a nonactivated, resting state with no collagen nor IAC-1 binding; (ii) an intermediate state, induced by outside manipulation, with collagen but no IAC-1 binding; and (iii) a fully activated state, induced after inside-out stimulation, with both collagen and IAC-1 binding. Moreover, these different conformational states of α2β1 are dependent on the cell type where α2β1 is expressed, as IAC-1 binding to peripheral blood mononuclear cells and Jurkat cells could also be induced by outside manipulation, in contrast to platelets and α2β1-expressing Chinese hamster ovary cells. Finally, we revealed a functional relevance for these different conformational states because the conformation of α2β1, induced after outside manipulation, resulted in significantly more cell spreading on coated collagen compared with nonactivated or inside-out stimulated cells.",
author = "{Van De Walle}, {Gerlinde R.} and Karen Vanhoorelbeke and Zs. Majer and Eszter Illy{\'e}s and Johan Baert and Inge Pareyn and Hans Deckmyn",
year = "2005",
month = "11",
day = "4",
doi = "10.1074/jbc.M508148200",
language = "English",
volume = "280",
pages = "36873--36882",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "44",

}

TY - JOUR

T1 - Two functional active conformations of the integrin α2β1, depending on activation condition and cell type

AU - Van De Walle, Gerlinde R.

AU - Vanhoorelbeke, Karen

AU - Majer, Zs.

AU - Illyés, Eszter

AU - Baert, Johan

AU - Pareyn, Inge

AU - Deckmyn, Hans

PY - 2005/11/4

Y1 - 2005/11/4

N2 - For several integrins, the existence of multiple conformational states has been studied intensively. For the integrin α2β1, a major collagen receptor on platelets and other cell types, however, no such experimental data were available thus far. Recently, our group has developed a monoclonal antibody IAC-1 sensitive to the molecular conformation of α2β1 because it only binds to the activated state of α2β1 on platelets, induced upon inside-out signaling. By investigating IAC-1 binding in combination with collagen binding after inside-out stimulation and outside manipulation, we demonstrated the existence of three different conformations of α2β1 on platelets and Chinese hamster ovary cells as follows: (i) a nonactivated, resting state with no collagen nor IAC-1 binding; (ii) an intermediate state, induced by outside manipulation, with collagen but no IAC-1 binding; and (iii) a fully activated state, induced after inside-out stimulation, with both collagen and IAC-1 binding. Moreover, these different conformational states of α2β1 are dependent on the cell type where α2β1 is expressed, as IAC-1 binding to peripheral blood mononuclear cells and Jurkat cells could also be induced by outside manipulation, in contrast to platelets and α2β1-expressing Chinese hamster ovary cells. Finally, we revealed a functional relevance for these different conformational states because the conformation of α2β1, induced after outside manipulation, resulted in significantly more cell spreading on coated collagen compared with nonactivated or inside-out stimulated cells.

AB - For several integrins, the existence of multiple conformational states has been studied intensively. For the integrin α2β1, a major collagen receptor on platelets and other cell types, however, no such experimental data were available thus far. Recently, our group has developed a monoclonal antibody IAC-1 sensitive to the molecular conformation of α2β1 because it only binds to the activated state of α2β1 on platelets, induced upon inside-out signaling. By investigating IAC-1 binding in combination with collagen binding after inside-out stimulation and outside manipulation, we demonstrated the existence of three different conformations of α2β1 on platelets and Chinese hamster ovary cells as follows: (i) a nonactivated, resting state with no collagen nor IAC-1 binding; (ii) an intermediate state, induced by outside manipulation, with collagen but no IAC-1 binding; and (iii) a fully activated state, induced after inside-out stimulation, with both collagen and IAC-1 binding. Moreover, these different conformational states of α2β1 are dependent on the cell type where α2β1 is expressed, as IAC-1 binding to peripheral blood mononuclear cells and Jurkat cells could also be induced by outside manipulation, in contrast to platelets and α2β1-expressing Chinese hamster ovary cells. Finally, we revealed a functional relevance for these different conformational states because the conformation of α2β1, induced after outside manipulation, resulted in significantly more cell spreading on coated collagen compared with nonactivated or inside-out stimulated cells.

UR - http://www.scopus.com/inward/record.url?scp=27744564167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744564167&partnerID=8YFLogxK

U2 - 10.1074/jbc.M508148200

DO - 10.1074/jbc.M508148200

M3 - Article

C2 - 16103112

AN - SCOPUS:27744564167

VL - 280

SP - 36873

EP - 36882

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 44

ER -