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Vol. 11, Issue 12, 4259-4275, December 2000
and§
*Departments of Anatomy and Medicine, University of California, San
Francisco, San Francisco, California 94143-0452;
Epithelial cyst and tubule formation are critical processes that
involve transient, highly choreographed changes in cell polarity. Factors controlling these changes in polarity are largely unknown. One
candidate factor is the highly conserved eight-member protein complex
called the exocyst. We show that during tubulogenesis in an in vitro
model system the exocyst relocalized along growing tubules consistent
with changes in cell polarity. In yeast, the exocyst subunit Sec10p is
a crucial component linking polarized exocytic vesicles with the rest
of the exocyst complex and, ultimately, the plasma membrane. When the
exocyst subunit human Sec10 was exogenously expressed in
epithelial Madin-Darby canine kidney cells, there was a selective
increase in the synthesis and delivery of apical and basolateral
secretory proteins and a basolateral plasma membrane protein, but not
an apical plasma membrane protein. Overexpression of human Sec10
resulted in more efficient and rapid cyst formation and increased
tubule formation upon stimulation with hepatocyte growth factor. We
conclude that the exocyst plays a central role in the development of
epithelial cysts and tubules.
Department of Cell Biology, Yale University School of
Medicine, New Haven, Connecticut 06520-8002; and
Departments of Anatomy, Biochemistry, and Biophysics,
and the Cardiovascular Research Institute, University of California,
San Francisco, San Francisco, California 94143-0452
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