Chromaffin cells exocytosis

Michelena P, de la Fuente MT, Vega T et al (1997) Drastic facilitation by a-latrotoxin of bovine chromaffin cell exocytosis without measurable enhancement of Ca2+ entry or [Ca2+]i. J Physiol (Lond) 502 481-96... 

Amatore C, Arbault S, Bonifas I, Bouret Y, Erard M, et al. 2005. Correlation between vesicle quantal size and fusion pore chromaffin cell exocytosis. Biophys J 88 4411-4420. 

In this lecture we will be concerned by exocytosis of neurotransmitters by chromaffin cells. These cells, located above kidneys, produce the adrenaline burst which induces fast body reactions they are used in neurosciences as standard models for the study of exocytosis by catecholaminergic neurons. Prior to exocytosis, adrenaline is contained at highly concentrated solutions into a polyelectrolyte gel matrix packed into small vesicles present in the cell cytoplasm and brought by the cytoskeleton near the cell outer membrane. Stimulation of the cell by divalent ions induces the fusion of the vesicles membrane with that of the cell and hence the release of the intravesicular content into the outer-cytoplasmic region. 

Steiner, J.A., Hortsmann, H. and Aimers, W. (1997) Transport, docking and exocytosis of single secretory granules in live chromaffin cells. Nature, 388, 474A78. 

The SNAREs involved in the fusion of synaptic vesicles and of secretory granules in neuroendocrine cells, referred to as neuronal SNAREs, have been intensely studied and serve as a paradigm for all SNAREs. They include syntaxin 1A and SNAP-25 at the presynaptic membrane and synaptobrevin 2 (also referred to as VAMP 2) at the vesicle membrane. Their importance for synaptic neurotransmission is documented by the fact that the block in neurotransmitter release caused by botulinum and tetanus neurotoxins is due to proteolysis of the neuronal SNAREs (Schiavo et al. 2000). Genetic deletion of these SNAREs confirmed their essential role in the last steps of neurotransmitter release. Intriguingly, analysis of chromaffin cells from KO mice lacking synaptobrevin or SNAP-25 showed that these proteins can be at least partially substituted by SNAP-23 and cellubrevin, respectively (Sorensen et al. 2003 Borisovska et al. 2005), i.e., the corresponding SNAREs involved in constitutive exocytosis. 

Criado M, Gil A, Viniegra S, Gutierrez LM (1999) A single amino acid near the C terminus of the synaptosome associated protein of 25 kKa (SNAP-25) is essential for exocytosis in chromaffin cells. Proc Natl Acad Sci USA 96 7256-61... 

O Sullivan G, Mohammed N, Foran P, Lawrence G, Dolly O (1999) Rescue of exocytosis in botulinum toxin A-poisoned chromaffin cells by expression of cleavage-resistant SNAP-25. Identification of the minimal essential C-terminal residues. J Biol Chem 274 36897-904 Oberg SG, Kelly RB (1976) The mechanism of beta-bungarotoxin action. I. modification of transmitter release at the neuromuscular junction. J Neurobiol 7 129 11 Ohishi I, Sugii S, Sakaguchi G (1977) Oral toxicities of Clostridium botulinum toxins in response to molecular size. Infect Immun 16 107-9... 

Based on the results of a-LTX mutagenesis, strong correlation exists between pore formation and stimulation of Ca2+-dependent exocytosis from neuroendocrine cells. However, in some experiments with chromaffin cells, a-LTX action does not involve Ca2+ entry (Michelena et al. 1997). In addition, a-LTX sensitizes chromaffin cells to Ca2+ even when the cells are permeabilized and toxin pores should have no effect this involves protein kinase C (PKC) activation (Bittner and Holz 2000). Furthermore, the ability of a-LTXN4C to induce Ca2+-dependent exocytosis without forming pores implicates a stimulating mechanism other than pore formation. 

Graham ME, Fisher RJ, Burgoyne RD (2000) Measurement of exocytosis by amperometry in adrenal chromaffin cells effects of clostridial neurotoxins and activation of protein kinase C on fusion pore kinetics. Biochimie 82 469-79... 

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... 

Morgan A, Burgoyne RD (1992) Interaction between protein kinase C and Exol (14-3-3 protein) and its relevance to exocytosis in permeabilized adrenal chromaffin cells. Biochem J 286 807-11... 

Nobles M, Benians A, Tinker A (2005) Heterotrimeric G proteins precouple with G protein-coupled receptors in living cells. Proc Natl Acad Sci USA 102 18706-11 Ohara-Imaizumi M, Kameyama K, Kawae N et al (1992) Regulatory role of the GTP-binding protein, G(o), in the mechanism of exocytosis in adrenal chromaffin cells. J Neurochem... 

Terbush DR, Holz RW (1990) Activation of protein kinase C is not required for exocytosis from bovine adrenal chromaffin cells. The effects of protein kinase C(19-31), Ca/CaM kinase 11(291— 317), and staurosporine. J Biol Chem 265 21179-84 Tesmer VM, Kawano T, Shankaranarayanan A et al (2005) Snapshot of activated G proteins at the membrane the Galphaq-GRK2-Gbetagamma complex. Science 310 1686-90 Thakur P, Stevens DR, Sheng ZH et al (2004) Effects of PKA-mediated phosphorylation of Snapin on synaptic transmission in cultured hippocampal neurons. J Neurosci 24 6476-81 Thompson SM, Capogna M, Scanziani M (1993) Presynaptic inhibition in the hippocampus. Trends Neurosci 16 222-7... 

Liang M, Eason MG, Jewell-Motz EA et al (1998) Phosphorylation and functional desensitisation of the a2A-adrenergic receptor by protein kinase C. Mol Pharmacol 54 44-9 Lim W, Kim SJ, Yan HD et al (1997) Ca2+-channel dependent and -independent inhibition of exocytosis by extracellular ATP in voltage-clamped rat adrenal chromaffin cells. Pflugers Arch 435 34 12... 

Garcia AG, Albillos A, Cano-Abad MF, Garcia-Palomero E, Hernandez-Guijo M, Herrero CJ, Lomax RB, Gandia L (1998) Calcium channels for exocytosis in chromaffin cells. Adv Pharmacol 42 91 1... 

Morgan, A., and Burgoyne, R. D. (1997). Common mechanisms for regulated exocytosis in the chromaffin cell and the synapse. Semin. CellDev. Biol. 8, 141—149. 

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