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Title: Two functional active conformations of the integrin alpha 2 beta 1, depending on activation condition and cell type
Authors: Van de Walle, Gerlinde ×
Vanhoorelbeke, Karen
Majer, Zsuzsa
Illyes, Eszter
Baert, Johan
Pareyn, Inge
Deckmyn, Hans #
Issue Date: Nov-2005
Publisher: Amer soc biochemistry molecular biology inc
Series Title: Journal of Biological Chemistry vol:280 issue:44 pages:36873-36882
Abstract: For several integrins, the existence of multiple conformational states has been studied intensively. For the integrin alpha 2 beta 1, 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 alpha 2 beta 1 because it only binds to the activated state of alpha 2 beta 1 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 alpha 2 beta 1 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 alpha 2 beta 1 are dependent on the cell type where alpha 2 beta 1 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 alpha 2 beta 1-expressing Chinese hamster ovary cells. Finally, we revealed a functional relevance for these different conformational states because the conformation of alpha 2 beta 1, induced after outside manipulation, resulted in significantly more cell spreading on coated collagen compared with nonactivated or inside-out stimulated cells.
Description: Subfaculteit Wetenschappen Campus Kortrijk. Interdisciplinair Research centrum Campus Kortrijk (IRC) Faculteit Geneeskunde. Subfaculteit Geneeskunde Campus Kortrijk. Histologie Campus Kortrijk.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
Chemistry, Campus Kulak Kortrijk
× corresponding author
# (joint) last author

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