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J. Biol. Chem., Vol. 266, Issue 24, 15598-15601, 08, 1991
A Wang, DS Cohen, E Palmer and D Sheppard
Fibronectin is a multifunctional protein that is synthesized in several
different forms that result from alternative splicing of mRNA. Although
expression of splicing variants appears to be both developmentally
regulated and tissue-specific, the functional significance of these
isoforms is largely unknown. We found that cultured airway epithelial cells
vectorially secrete two distinct species of fibronectin, one which contains
the alternatively spliced EIIIA region (EIIIA+) and one in which the EIIIA
segment is spliced out (EIIIA-). Fibronectin containing the EIIIA region is
preferentially secreted apically. Although both apical and basal
stimulation with transforming growth factor beta 1 increased fibronectin
synthesis, the secretory response differed depending on which surface was
being stimulated. Apical secretion of fibronectin and expression of EIIIA+
fibronectin mRNA increased only after apical stimulation. These data
demonstrate a novel mechanism for the polarized regulation of targeted
secretion and alternative splicing of fibronectin and suggest that the
EIIIA segment may act as a targeting signal for the vectorial secretion of
fibronectin.
Polarized regulation of fibronectin secretion and alternative splicing by transforming growth factor
Lung Biology Center, San Francisco General Hospital, California 94143.
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