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Vol. 13, Issue 3, 830-846, March 2002
and
*Renal-Electrolyte Division, Department of Medicine, Laboratory of
Epithelial Cell Biology, and Department of Cell Biology and Physiology,
University of Pittsburgh, Pittsburgh, Pennsylvania 15261; and
The epithelium of the urinary bladder must maintain a highly
impermeable barrier despite large variations in urine volume during
bladder filling and voiding. To study how the epithelium accommodates
these volume changes, we mounted bladder tissue in modified Ussing
chambers and subjected the tissue to mechanical stretch. Stretching the
tissue for 5 h resulted in a 50% increase in lumenal surface area
(from ~2900 to 4300 µm2), exocytosis of a population of
discoidal vesicles located in the apical cytoplasm of the superficial
umbrella cells, and release of secretory proteins. Surprisingly,
stretch also induced endocytosis of apical membrane and 100% of
biotin-labeled membrane was internalized within 5 min after stretch.
The endocytosed membrane was delivered to lysosomes and degraded by a
leupeptin-sensitive pathway. Last, we show that the exocytic events
were mediated, in part, by a cyclic adenosine monophosphate, protein
kinase A-dependent process. Our results indicate that stretch modulates
mucosal surface area by coordinating both exocytosis and endocytosis at
the apical membrane of umbrella cells and provide insight into the
mechanism of how mechanical forces regulate membrane traffic in
nonexcitable cells.
Department of Statistics, University of Pittsburgh,
Pittsburgh, Pennsylvania 15260
These authors contributed equally to this work and
are listed in no particular order.
§
Corresponding author. E-mail address:
gla6{at}pitt.edu.
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