The Exocyst Complex in Health and Disease

Abstract

Exocytosis involves the fusion of intracellular secretory vesicles with the plasma membrane, thereby delivering integral membrane proteins to the cell surface and releasing material into the extracellular space. Importantly, exocytosis also provides a source of lipid moieties for membrane extension. The tethering of the secretory vesicle before docking and fusion with the plasma membrane is mediated by the exocyst complex, an evolutionary conserved octameric complex of proteins. Recent findings indicate that the exocyst complex also takes part in other intra-cellular processes besides secretion. These various functions seem to converge toward defining a direction of membrane growth in a range of systems from fungi to plants and from neurons to cilia. In this review we summarize the current knowledge of exocyst function in cell polarity, signaling and cell-cell communication and discuss implications for plant and animal health and disease.

Analysis of Exocyst Subunit EXO70 Family Reveals Distinct Membrane Polar Domains in Tobacco Pollen Tubes

“…One of the key components regulating cell polarity is the exocyst complex. It is a heterooctameric protein complex (TerBush et al, 1996) that is shared across eukaryotes (Vaškovi cová et al, 2013;Martin-Urdiroz et al, 2016) and that tethers secretory vesicles to the plasma membrane (PM) and regulates their subsequent fusion. In animal and yeast model systems, many molecular interactions involved in exocyst function have already been discovered: EXO70 and SEC3 drive exocyst to the target site by interaction with phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and small GTPases of the Rho family (He et al, 2007;Liu et al, 2007;Wu et al, 2010;Pleskot et al, 2015), both budding yeast (Saccharomyces cerevisiae) Sec15p (France et al, 2006) and Exo70p interact with the cell polarity determinant Bem1p (Liu and Novick, 2014), SEC15 interacts with secretory vesicle-associated Rab GTPases (Wu et al, 2005) and promotes myosin motor release after vesicle fusion with the PM (Donovan and Bretscher, 2015), and budding yeast Sec6p binds SNARE proteins and promotes SNARE complex assembly (Dubuke et al, 2015) and also binds the SNARE interactor Sec1p (Morgera et al, 2012).…”

The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

“…A highly important exocytotic processes is associated with vesicular neurotransmitter release at the presynaptic site [373]. These unique membrane-bound vesicles contain not only neurotransmitters but also soluble proteins, lipids and ATP to be secreted into the synaptic cleft [374,375]. Several families of vesicle proteins have been characterized among which synaptophysin, synapsins, synaptobrevins andsynaptotagmins are most common [372].…”

Regulation of plasma membrane expansion during axon formation

“…In both yeast and mammalian cells the exocyst, a complex of eight polypeptides, is involved in docking and tethering exocytic vesicles at sites of fusion (Lipschutz and Mostov, 2002;EauClaire and Guo, 2003;Martin-Urdiroz et al, 2016). The exocyst complex has been implicated in a wide variety of cell functions, including morphogenesis, migration and tumor invasion; its subunits are direct targets of several small GTPases, such as Rabs, Cdc42, TC10 (a Cdc42 homolog), and RalGT-Pases (Wu and Guo, 2015;Zhu et al, 2017) that result in exocyst activation.…”