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 prior to 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.Polarized exocytosis is essential for a wide range of biological processes such as cell growth, morphogenesis, and cell migration. Exocytosis is accomplished by the fusion of secretory vesicles with the plasma membrane catalyzed by the assembly of the SNARE complex. Prior to membrane fusion, additional proteins mediate the initial interaction between the vesicles and the acceptor membrane, a process known as "vesicle tethering". Tethering of secretory vesicles to the plasma membrane is thought to be mediated by the exocyst, an evolutionarily conserved octameric protein complex consisting of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 [[1**] and [2**]]. Recent studies from different disciplines have led to significant advance in our understanding of the exocyst in various eukaryotic systems and physiological processes. Here we review the most recent progresses in the field, focusing on the role of the exocyst in exocytosis. The structure of the exocystUnderstanding the structure of the exocyst may provide important insight into the molecular mechanism of the exocyst function. So far, partial crystal structures of four exocyst components have been solved [3]. These include the near full-length yeast and mouse Exo70 [[4**], [5] and [6]], and the C-terminal domains of Drosophila Sec15 [7], yeast Exo84 [4**], and yeast Sec6 [8**]. While these exocyst components share little sequence homology, they all display rod-like structures composed of two or more consecutively packed helical bundles, with each bundle consisting of three to five α-helices linked by loops. The structural conservation among exocyst components suggests that they evolved from a common ancestor. In addition, several exocyst components have been found to share distant sequence homology with subunits of two other tethering complexes that function at the Golgi apparatus, the conserved oligomeric Golgi (COG) complex and the Golgi-associated retrograde protein (GARP) complex [9]. The crystal structure of the COG subunit COG2 shows a helical bundle structure similar to that of the exocyst components [10]. These findings suggest that the exocyst, the COG and the GARP *Correspondence: guowei@sas.upenn.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The ...

Membrane Organization and Dynamics in Cell Polarity

“…Biochemical and genetic analyses in yeast suggest that the exocyst functions at a step after the delivery of secretory vesicles to the plasma membrane but before the assembly of the SNARE complex and vesicle fusion (Grote et al 2000). Thus, the exocyst complex likely functions as a tether that mediates the initial contact between the secretory vesicles and the plasma membrane before docking and fusion (Pfeffer 1999;Hsu et al 2004;He and Guo 2009).…”

Signaling Events in Pollen Acceptance or Rejection in the Arabidopsis Species

“…Some of the exocyst subunit genes are present in multiple copies in plant genomes, and Exo70A1 is one member of the Exo70 gene family in A. thaliana (Synek et al 2006 ;Chong et al 2010 ). In yeast and animal systems, the exocyst was determined to act as a tethering complex to dock secretory vesicles to the plasma membrane for polar secretion, and various small GTPases have been found to interact with exocyst subunits to regulate the assembly, localization, and function of this complex (reviewed in He and Guo 2009 ;Heider and Munson 2012 ). Once the vesicles have been tethered at the plasma membrane by the exocyst complex, the SNARE complex catalyzes the fusion of the secretory vesicle to the plasma membrane (Whyte and Munro 2002 ).…”

Cell surface dynamics – how Rho GTPases orchestrate the interplay between the plasma membrane and the cortical cytoskeleton

“…In epithelial cells, they operate on the lateral and not on the luminal surface. Therefore, Rho and the exocysts are essential for establishing polarity (Mellman and Nelson, 2008;He and Guo, 2009). In developing neurons, Rho GTPases and the exocyst induce axon specification and outgrowth but have no role in the regulated discharge of synaptic vesicles (Dupraz et al, 2009;Schwenger and Kuner, 2010).…”