Heterologous expression of alpha 1-integrin cDNA generates variable ligand specificities and alterations in cell shape.
Integrins can mediate a diverse variety of functions that are regulated by unknown mechanisms. Integrin alpha 1 beta 1 can serve as a receptor for laminin-1 and collagen in certain cell types, but is a receptor for only collagen in others. To examine the molecular basis of this difference in specificity, three cell types were transfected with cDNA for the rat alpha 1 subunit. Following transfection with rat alpha 1, pluripotential hematopoietic human K562 cells exhibited alpha 1 beta 1-dependent attachment to collagen IV, but not laminin-1, unless activating antibody TS2/16 was added. The attachment to collagen IV stimulated the elaboration of a spread morphology resembling a differentiated megakarocyte with extensive processes which were absent in response to all other substrates. When MRC-5 cells, a human fibroblastic cell, or RD cells, a human rhabdomyosarcoma line, were transfected with the identical alpha 1-integrin construct, rat alpha 1 beta 1-dependent attachment to both collagen IV and laminin-1 was seen. Therefore differences in ligand specificity can be generated by translation of an identical integrin alpha 1 beta 1 mRNA in different cell types. Despite differences in ligand binding, alpha 1 cDNA-transfected K562 and RD cells express an alpha 1 subunit that appears to be antigenically and electrophoretically similar. Small differences in glycosylation were apparent, and correlated with changes in ligand specificity. Together these results show for the first time that identical cDNAs, absent activating antibodies or other manipulations, can change ligand selectivity and better establish the importance of cellular context in determining integrin function. Moreover they show that select integrins can shift the differentiated state of pluripotential cells.
Wong
L D
LD
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Sondheim
A B
AB
Zachow
K R
KR
Reichardt
L F
LF
Ignatius
M J
MJ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D018076:DNA, Complementary; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039423:Integrin alpha1; D008024:Ligands; D051381:Rats; D014162:Transfection
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D005353:Fibronectins; D039423:Integrin alpha1; D008024:Ligands; D003094:Collagen