The alphavbeta3 integrin regulates alpha5beta1-mediated cell migration toward fibronectin.
This study examines the interactions of alphavbeta3 and alpha5beta1 in the regulation of cell migration. Human embryonic kidney (HEK) 293 cells that express alpha5beta1 endogenously were transfected with alphavbeta3 and beta3 mutants, and their attachment and migration to fibronectin (Fn) and vitronectin (Vn) were measured. An alphavbeta3 blocking antibody and the alphavbeta3 ligand cyclic G-Pen-GRGDSPC-A inhibited alpha5beta1-mediated migration toward Fn, but not attachment to Fn. This function was alphavbeta3-specific since alphavbeta5 transfection and alphavbeta5 blocking antibody did not produce this effect. Mutations introduced into the beta3 integrin subunit to dissect this phenomenon revealed the following. Disruption of the ligand binding domain by the Glanzmann thrombasthenia mutation beta3-D119Y constitutively abolished migration toward both Vn and Fn, and attachment to Vn but not to Fn. Insertion of the Glanzmann mutation beta3-S752P into the cytoplasmic domain or its truncation (beta3-Delta717) abolished binding to Vn but not to Fn. Inhibition of migration toward Fn was inhibited in these cells by alphavbeta3 blocking antibody. alphavbeta3-mediated inhibition was, however, abolished by truncation of the transmembrane domain (beta3-Delta693). These findings demonstrate alphavbeta3 regulation of alpha5beta1-mediated cell migration and suggest that the beta3 transmembrane domain is essential for this function.
Simon
K O
KO
Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Nutt
E M
EM
Abraham
D G
DG
Rodan
G A
GA
Duong
L T
LT
D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D017354:Point Mutation; D017469:Receptors, Fibronectin / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D005353:Fibronectins; D009842:Oligopeptides; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; C047981:arginyl-glycyl-aspartic acid