**6. Acknowledgments**

Work described in this chapter was supported by NIH NIDCR grants DE012205 and DE019243.

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**4** 

**Molecular Machinery Regulating Exocytosis** 

*School of Pharmacy and Medical Sciences, Sansom Institute for Health Research,* 

Exocytosis is the major intracellular route for the delivery of proteins and lipids to the plasma membrane and the means by which vesicular contents are released into the extracellular space. The anterograde trafficking of vesicles to the plasma membrane is vital for membrane expansion during cell division; cell growth and migration; the delivery of specialised molecules to establish cell polarity; cell-to-cell communication; neurotransmission and the secretion of response factors such as hormones, cytokines and antimicrobial peptides. There are two major trafficking routes in eukaryotic cells, which are referred to as constitutive and regulated (Ory & Gasman, 2011). Constitutive exocytosis involves the steady state delivery of secretory carrier vesicles from the endoplasmic reticulum via the Golgi apparatus to the plasma membrane (Lacy & Stow, 2011). Regulated or granule-mediated exocytosis involves a specific trigger, usually a burst of intracellular calcium following an extrinsic stimulus. This system is utilized for secretion in neuronal cells and other specialist secretory cells, such as neuroendocrine, endocrine and exocrine cells (Burgoyne & Morgan, 2003; Jolly & Sattentau, 2007; Lacy & Stow, 2011). Regulated exocytosis enables a rapid response from a subpopulation of vesicles already primed and competent for fusion (Manjithaya & Subramani, 2011; Nickel & Seedorf, 2008; Nickel, 2010). Regulated exocytosis is also used for polarised traffic of vesicular membrane and cargo to specific spatial landmarks and this is particularly important during times of dramatic change in cell morphology, such as cell division, cell motility, phagocytosis

Regulated exocytosis involves the shuttling of carrier vesicles between vesicular compartments, as they are transported towards the plasma membrane. Each step in this process requires the fission of a vesicle from a donor compartment. This carrier vesicle is then targeted/trafficked to an acceptor compartment where docking and fusion takes place, and the cargo is either unloaded or further processed (Bonifacino & Glick, 2004). These fission and fusion steps are repeated until the cargo reaches the plasma membrane (Bonifacino & Glick, 2004). This sequential trafficking of secretory vesicles is orchestrated by a complex set of molecular machinery including: small GTPases of the Ral, Rab and Rho subfamilies that regulate the processes of vesicle formation, traffic and fusion; the

**1. Introduction** 

and axonal outgrowth.

R.D. Brooks, G.N. Borlace, M.J. Prodoehl and D.A. Brooks

*Mechanisms in Cell Biology and Diseases Research Group,* 

T. Shandala, R. Kakavanos-Plew, Y.S. Ng, C. Bader, A. Sorvina, E.J. Parkinson-Lawrence,

*University of South Australia* 

*Australia* 

