The exocyst complex in polarized exocytosis

Abstract

The exocyst is an octameric protein complex, which mediates the tethering of post-Golgi secretory vesicles to the plasma membrane before exocytic fusion. The exocyst assembles by side-by-side packing of rod-shaped subunits composed of helical bundles. The targeting of secretory vesicles to the plasma membrane involves direct interactions of the exocyst with PI(4,5)P(2). In addition, a number of small GTP-binding proteins interact with components of the exocyst and regulate the assembly, localization, and function of this complex. Here we review the recent advances in the field, focusing on the function of the exocyst in polarized exocytosis.

Figure 1. A model for the function of the exocyst complex in tethering the secretory vesicles to the plasma membrane in yeast

Sec3 and Exo70 directly associate with PI(4,5)P₂ (shown in red) in the plasma membrane via their positively charged residues (“+++”). Exo70 and Sec3 interact with the rest of the exocyst subunits riding on the arriving secretory vesicles. Another exocyst subunit Sec15 directly binds to the GTP-bound form of Rab GTPase Sec4, which is peripherally associated with the secretory vesicle and regulates the assembly of the exocyst complex. The assembly of the exocyst serves to tether the vesicles to the plasma membrane site specified by Sec3 and Exo70. The exocyst may also regulate the assembly of the SNARE complex through direct or indirect interactions. The exocyst is also regulated by the Rho GTPases Cdc42, Rho1, and Rho3. Cdc42 and Rho1 interact with Sec3 and control the polarized localization of the exocyst. Rho3 interacts with Exo70; however, the functional implication of this interaction is not clear. “3”: Sec3; “5”: Sec5; “6”: Sec6; “8”: Sec8; “10”: Sec10; “15”: Sec15; “70”: Exo70; “84”: Exo84. Sso1/2 and Sec9 are the t-SNAREs and Snc1/2 are the v-SNAREs for exocytosis at the plasma membrane in yeast.