Triggered Exocytosis

Most cells release macromolecules to the exterior by exocytosis. This process is also involved in membrane remodeling, when the components synthesized in the Colgi apparatus are carried in vesicles to the plasma membrane. The signal for exocytosis is often a hormone which, when it binds to a cell-surface receptor, induces a local and transient change in Ca concentration. Ca triggers exocytosis. Figure 41—16 provides a comparison of the mechanisms of exocytosis and endocytosis. 

In addition to its role as a bone component, calcium functions as a signaling substance. Ca "" ions act as second messengers in signal transduction pathways (see p. 386), they trigger exocytosis (see p. 228) and muscle contraction (see p. 334), and they are indispensable as cofactors in blood coagulation (see p. 290). Many enzymes also require Ca "" for their activity. The intracellular and extracellular concentrations of Ca "" are strictly regulated in order to make these functions possible (see B, C, and p.388). 

Huettner JE, Bean BP (1988) Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801 selective binding to open channels. Proc Natl Acad Sd U S A 85 1307-11 Jackson MB, Chapman ER (2006) Fusion pores and fusion machines in Ca2+-triggered exocytosis. Annu Rev Biophys Biomol Struct 35 135-60 Kavalali ET, Klingauf J, Tsien RW (1999) Properties of fast endocytosis at hippocampal synapses. 

Aristotle (350 B.C.) History of Animals. In Barnes J (ed) The complete works of Aristotle The revised Oxford translation, 1984, Princeton, Princeton University Press Ashton AC, Rahman MA, Volynski KE et al (2000) Tetramerisation of a-latrotoxin by divalent cations is responsible for toxin-induced non-vesicular release and contributes to the Ca2+-dependent vesicular exocytosis from synaptosomes. Biochimie 82 453-68 Ashton AC, Volynski KE, Lelianova VG et al (2001) a-Latrotoxin, acting via two Ca2+-dependent pathways, triggers exocytosis of two pools of synaptic vesicles. J Biol Chem 276 44695-703 Auger C, Marty A (1997) Heterogeneity of functional synaptic parameters among single release sites. Neuron 19 139-50... 

Dudanova I, Sedej S, Ahmad M et al (2006) Important contribution of a-neurexins to Ca2+-triggered exocytosis of secretory granules. J Neurosci 26 10599-613 Fesce R, Segal JR, Ceccarelli B et al (1986) Effects of black widow spider venom and Ca2+ on quantal secretion at the frog neuromuscular junction. J Gen Physiol 88 59-81 Filippov AK, Tertishnikova SM, Alekseev AE et al (1994) Mechanism of a-latrotoxin action as revealed by patch-clamp experiments on Xenopus oocytes injected with rat brain messenger RNA. Neuroscience 61 179-89... 

Sugita S, Ichtchenko K, Khvotchev M et al (1998) a-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. G-protein coupling not required for triggering exocytosis. J Biol Chem 273 32715-24 Sugita S, Khvochtev M, Sfldhof TC (1999) Neurexins are functional a-latrotoxin receptors. Neuron 22 489-96... 

Chaki S, Muramatsu M, Otomo S (1994) Involvement of protein kinase C activation in regulation of acetylcholine release from rat hippocampal slices by minaprine. Neurochem Int 24 37-41 Chameau P, Van d, V, Fossier P et al (2001) Ryanodine-, IP3- and NAADP-dependent calcium stores control acetylcholine release. Pflugers Arch 443 289-96 Chapman ER (2002) Synaptotagmin a Ca(2+) sensor that triggers exocytosis Nat Rev Mol Cell Biol 3 498-508... 

Jackson, M.B., Chapman, E.R. Fusion pores and fusion machines in Ca2+-triggered exocytosis. Annu. Rev Biophys. Biomol. Struct. 2006, 35 135-160. 

Figure 5.12. Regulation of insulin secretion by glucose in the pancreatic islet p-cell. An increase in glucose will yield increased ATP levels, which in turn will close the Kj. channels and partially depolarize the membrane. Opening of voltage-gated Ca channels will trigger exocytosis of insulin.

Figure 7.3. Mechanism of transmitter release, a Thepresynap-tic action potential opens voltage-gated Ca channels. Ca triggers exocytosis of neurotransmitters stored in piesynaptic vesicles. b Some proteins (out of mat r more) that are involved in exocytosis. Ca is involved at multiple stages. By binding to calmodulin (CaM), it promotes phosphorylation of synapsin, which primes the transmitter vesicle but does not immediately lead to exocytosis. Adhesion of primed vesicles to the presynap-tic membrane is mediated by synaptobrevin and other SNARE proteins. Synaptotagmin is activated directly by Ca and participates in the final step of secretiom...

Zhang X, Kim-Miller MJ, Fukuda M, Kowalchyk JA, Martin TF. Ca2 + -dependent synaptotagmin binding to SNAP-25 is essential for Ca2-b-triggered exocytosis. Neuron 2002 34 599-611. 

Chapman ER. Synaptotagmin a Ca(2 -f) sensor that triggers exocytosis ... 

Chapman ER (2002) Synaptotagmin A Ca(2-i-) sensor that triggers exocytosis Nat Rev Mol Cell Biol 3 498-508. 

SNAP-25 and syntaxin form a stoichiometric complex. This complex can bind one molecule of VAMP with high affinity. This trimeric SNARE complex is stable in sodium dodecylsulfate (Chapman et al., 1994 Hayashi etal., 1994, 1995). In the process of neuroexocytosis, SNARE complex formation precedes the recruitment of cytosolic and membrane protein components required for fusion of the lipid bilayers (Rothman, 1994 Sollner, 1995). It is likely that NSF-mediated hydrolysis of ATP provides energy for priming the neuroexocytotic apparatus. The primed system is now ready to trigger exocytosis upon calcium influx into the synapse. It is not yet established if the last step of neurotransmitter release takes place via a fusion pore or through a complete membrane fusion with lipid intermixing (Monk and Fernandez, 1994 Bruns and John, 1996). 

Parsons TD, Lenzi D, Aimers W, Roberts WM (1994) Calcium-triggered exocytosis and endocytosis in an isolated presynaptic cell capacitance measurements in saccular hair cells. Neuron 75 875-883. 

Chapman, E. R. 2002. Synaptotagmin a Ca " sensor that triggers exocytosis Nature Rev. Mol. Cell Biol. 3 498-508. 

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