Sec6/8 Complex Is Recruited to Cell–Cell Contacts and Specifies Transport Vesicle Delivery to the Basal-Lateral Membrane in Epithelial Cells

TLDR

The Sec6/8p complex is essential for establishing cell polarity in budding yeast by directing vesicle delivery to the bud tip. In MDCK epithelial cells, Sec6/8 homologs form a ~17S complex that is rapidly recruited to cell–cell contacts during calcium‑dependent adhesion, and Sec8 is required for delivery of LDL receptor to the basal‑lateral membrane but not for apical p75NTR, demonstrating that Sec6/8 recruitment is essential for epithelial polarity.

Abstract

In budding yeast, the Sec6/8p complex is essential for generating cell polarity by specifying vesicle delivery to the bud tip. We show that Sec6/8 homologs are components of a cytosolic, approximately 17S complex in nonpolarized MDCK epithelial cells. Upon initiation of calcium-dependent cell-cell adhesion, approximately 70% of Sec6/8 is rapidly (t(1/2) approximately 3-6 hr) recruited to sites of cell-cell contact. In streptolysin-O-permeabilized MDCK cells, Sec8 antibodies inhibit delivery of LDL receptor to the basal-lateral membrane, but not p75NTR to the apical membrane. These results indicate that lateral membrane recruitment of the Sec6/8 complex is a consequence of cell-cell adhesion and is essential for the biogenesis of epithelial cell surface polarity.