Exocyst is involved in cystogenesis and tubulogenesis and acts by modulating synthesis and delivery of basolateral plasma membrane and secretory proteins.
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.
Lipschutz
J H
JH
Department of Anatomy, University of California, San Francisco, San Francisco, California 94143-0452, USA.
Guo
W
W
O'Brien
L E
LE
Nguyen
Y H
YH
Novick
P
P
Mostov
K E
KE
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005656:Fungal Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D022142:Secretory Vesicles / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D014162:Transfection; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; C419575:EXOC5 protein, human; D005656:Fungal Proteins; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; C105132:SEC10 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins