Regulated Exocytosis

In electrically permeabilized insulin-secreting cells, the influence of soluble second messengers on exocytosis can be studied directly, since it is possible to dialyze such cells with respect to nucleotides and ions while cytosolic proteins are retained. In the presence of ATP, Ca stimulates insulin exocytosis with an EC50 of approximately 1.6 l/Vl (Vallar efal., 1987, Ullrich efal., 1990). This is in close agreement with the value for Ca -stimulated exocytosis in patch-clamped mouse P-cells obtained using the capacitance method (Bokvist ef al., 

In contrast to, cA/VtP is unable to stimulate exocytosis on its own, but potentiates Ca -induced exocytosis (Vallar efal., 1987). This is consistent with the role of cAMP-generating hormones as potentiators of insulin secretion. 

The mechanism by which epinephrine and other neurohormones inhibit insulin secretion involves pertussis toxin-sensitive G-proteins. These hormones exert multiple actions, all contributing to the marked reduction of stimulated insulin secretion (Ullrich and Wollheim, 1988, Lang ef al., 1993). They thus inhibit adenylyl cyclase activity, hyperpo-larize the membrane potential by increasing K conductance, and 

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During exocytosis, intracellular vesicles fuse with the plasmalemma. As a consequence, the vesicle components are incoiporated into the plasma membrane and the vesicle content is released into the extracellular space. We distinguish constitutive and regulated exocytosis. 

Regulated Exocytosis of Glutamate from Astrocytes can Modulate Synaptic Transmission... 

Kasai H (1999) Comparative biology of Ca -dependent exocytosis implications of kinetic diversity for secretory function. Trends Neurosci 22 88-93 Kasai H, Kishimoto T, Liu TT, Miyashita Y, Podini P, Grohovaz F, Meldolesi J (1999) Multiple and diverse forms of regulated exocytosis in wild-type and defective PC12 cells. Proc Natl... 

One characteristic of regulated exocytosis is the ability to store secretory vesicles in a reserve pool for utilization upon stimulation. In the presynaptic terminal, this principle is expanded to define multiple pools of synaptic vesicles a ready releasable pool, a recycled synaptic vesicle pool and a larger reserve pool. This reserve pool assures that neurotransmitter is available for release in response to even the highest physiological demands. Neurons can fire so many times per minute because synaptic vesicles from the ready releasable pool at a given synapse undergo exocytosis in response to a single action potential. 

Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E, Volterra A (2004) Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 7 613-620. 

Tomosyn is a soluble protein of 130 kDa with a C-terminal R-SNARE motif that is capable of replacing synaptobrevin in the neuronal SNARE complex. Most available data indicate that tomosyn negatively regulates exocytosis by competing with synaptobrevin in the formation of SNARE complexes (Brunger 2005), thereby leading to the inhibition of synaptic vesicle priming (McEwen et al. 2006). 

Burgoyne RD, Fisher RJ, Graham ME et al (2001) Control of membrane fusion dynamics during regulated exocytosis. Biochem Soc Trans 29 467-72 Burke BE, DeLorenzo RJ (1981) Ca2+- and calmodulin-stimulated endogenous phosphorylation of neurotubulin. Proc Natl Acad Sci USA 78 991-5... 

Loyet KM, Kowalchyk JA, Chaudhary A et al (1998) Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phos-phoinositide effector protein for regulated exocytosis. J Biol Chem 273 8337 13 Luscher C, Jan LY, Stoffel M et al (1997) G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron 19 687-95... 

Mirotznik RR, Zheng X, Stanley EF (2000) G-Protein types involved in calcium channel inhibition at a presynaptic nerve terminal. J Neurosci 20 7614—21 Misonou H, Ohara-Imaizumi M, Kumakura K (1997) Regulation of the priming of exocytosis and the dissociation of SNAP-25 and VAMP-2 in adrenal chromaffin cells. Neurosci Lett 232 182—4 Misonou H, Ohara-Imaizumi M, Murakami T et al (1998) Protein kinase C controls the priming step of regulated exocytosis in adrenal chromaffin cells. Cell Mol Neurobiol 18 379-90... 

Orita S, Naito A, Sakaguchi G et al (1997) Physical and functional interactions of Doc2 and Muncl3 in Ca2+-dependent exocytotic machinery. J Biol Chem 272 16081 4 Ozaki N, Shibasaki T, Kashima Y et al (2000) cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nat Cell Biol 2 805-11... 

Scholze T, Moskvina E, Mayer M et al (2002) Sympathoexcitation by bradykinin involves Ca2+-independent protein kinase C. J Neurosci 22 5823-32 Schwartz EJ, Blackmer T, Gerachshenko T et al (2007) Presynaptic G-protein-coupled receptors regulate synaptic cleft glutamate via transient vesicle fusion. J Neurosci 27 5857-68 Searl TJ, Silinsky EM (1998) Increases in acetylcholine release produced by phorbol esters are not mediated by protein kinase C at motor nerve endings. J Pharmacol Exp Ther 285 247-51 Seino S, Shibasaki T (2005) PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 85 1303 12... 

REGULATED EXOCYTOSIS FROM ASTROCYTES PHYSIOLOGICAL AND PATHOLOGICAL RELATED ASPECTS... 

The molecular mechanisms leading to release of gliotransmitters, especially glutamate, from glia are under debate. Accumulating evidence clearly indicates that astrocytes secrete numerous transmitters by Ca2+-dependent exocytosis. This review will discuss the mechanisms underlying the release of chemical transmitters from astrocytes with a particular emphasis to the regulated exocytosis processes. 

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