Integrin-mediated cell adhesion to type I collagen fibrils.
In the integrin family, the collagen receptors form a structurally and functionally distinct subgroup. Two members of this subgroup, alpha(1)beta(1) and alpha(2)beta(1) integrins, are known to bind to monomeric form of type I collagen. However, in tissues type I collagen monomers are organized into large fibrils immediately after they are released from cells. Here, we studied collagen fibril recognition by integrins. By an immunoelectron microscopy method we showed that integrin alpha(2)I domain is able to bind to classical D-banded type I collagen fibrils. However, according to the solid phase binding assay, the collagen fibril formation appeared to reduce integrin alpha(1)I and alpha(2)I domain avidity to collagen and to lower the number of putative alphaI domain binding sites on it. Respectively, cellular alpha(1)beta(1) integrin was able to mediate cell spreading significantly better on monomeric than on fibrillar type I collagen matrix, whereas alpha(2)beta(1) integrin appeared still to facilitate both cell spreading on fibrillar type I collagen matrix and also the contraction of fibrillar type I collagen gel. Additionally, alpha(2)beta(1) integrin promoted the integrin-mediated formation of long cellular projections typically induced by fibrillar collagen. Thus, these findings suggest that alpha(2)beta(1) integrin is a functional cellular receptor for type I collagen fibrils, whereas alpha(1)beta(1) integrin may only effectively bind type I collagen monomers. Furthermore, when the effect of soluble alphaI domains on type I collagen fibril formation was tested in vitro, the observations suggest that integrin type collagen receptors might guide or even promote pericellular collagen fibrillogenesis.
Jokinen
Johanna
J
Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä FI-40014, Finland.
Dadu
Elina
E
Nykvist
Petri
P
Käpylä
Jarmo
J
White
Daniel J
DJ
Ivaska
Johanna
J
Vehviläinen
Piia
P
Reunanen
Hilkka
H
Larjava
Hannu
H
Häkkinen
Lari
L
Heino
Jyrki
J
D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology*; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D039222:Integrin alpha1beta1 / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D024042:Collagen Type I; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D016023:Integrins; D011993:Recombinant Fusion Proteins