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(Received for publication, October 11, 1996, and in revised form, November 12, 1996)
From the Departments of Anatomy and Biochemistry and Biophysics,
Cardiovascular Research Institute, University of California,
San Francisco, California 94143-0452
Hepatocyte growth factor (HGF) and E-cadherin are
important for epithelial morphogenetic events. We examined the effects
of HGF on E-cadherin localization and interaction with 
-catenin in
polarized Madin-Darby canine kidney (MDCK) cell monolayers grown on
filters. Surface biotinylation experiments showed that HGF increases
apically accessible E-cadherin. Confocal immunofluorescence microscopy
of HGF-treated cells showed localization of E-cadherin at membrane
domains contacting the apical compartment and an increase in
accessibility of apically applied antibodies to lateral E-cadherin below the tight junction. Coimmunoprecipitation of
-catenin/E-cadherin complexes showed that the amount of E-cadherin
associated with -catenin increased during the first 24 h of HGF
treatment with a return to baseline values after 48 and 72 h.
Metabolic labeling showed that HGF increased the synthetic rate of
-catenin and the amount of newly synthesized E-cadherin associated
with immunoprecipitated -catenin, with the peak effect occurring
after 12 h of treatment and returning to baseline after 24 h.
HGF treatment inhibited transcytosis of immunoglobulin A by the
polymeric immunoglobulin receptor. We conclude that HGF treatment of
polarized MDCK cells grown on filters decreases cell polarity and
alters E-cadherin/-catenin interaction and synthesis.
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