L. Koivisto et al., THE SIZE OF THE INTRACELLULAR BETA-1-INTEGRIN PRECURSOR POOL REGULATES MATURATION OF BETA-1-INTEGRIN SUBUNIT AND ASSOCIATED ALPHA-SUBUNITS, Biochemical journal, 300, 1994, pp. 771-779
A large pool of precursor beta 1-integrin subunits is frequently found
intracellularly. During malignant transformation this pool often disa
ppears. Concomitantly, integrin-mediated cell-adhesion functions are d
isturbed, even though no change in the number of beta 1-integrin recep
tors on the cell surface can be observed. Here, we have studied the ro
le of an intracellular pre beta 1-integrin pool by transfecting human
MG-63 osteosarcoma cells with plasmid construction producing an antise
nse RNA for the beta 1-integrin subunit. Stable cell clones expressing
beta 1-integrin antisense RNA were shown to have a reduced intracellu
lar pool of pre-beta 1-integrin subunits. In the antisense-transfected
cells, the synthesis of the beta 1-integrin chain was reduced by 65%
compared with non-transfected or vector-transfected MG-63 cells. The d
ecreased synthesis of the beta 1-integrin chain was associated with ac
celerated maturation of the beta 1-integrin chain (half-maturation tim
e about 5 h in antisense-transfected cells compared with about 10.5 h
in control cells), whereas maturation of the alpha-integrin chain slow
ed down. The amount of beta 1-integrins on the cell surface, however,
remained unaltered. Cell clones with the largest decrease in the relat
ive amount of the pre-beta 1-integrin subunit also showed altered inte
grin function. They were found to synthesize fibronectin, but were una
ble to assemble it into a fibronectin matrix on the cell surface. Thus
we conclude that the repression of biosynthesis of the beta 1-integri
n chain leads to alterations in receptor maturation and may be connect
ed with altered receptor function.