Exocytosis control

Protein trafficking is the transport of proteins to their correct subcellular compartments or to the extracellular space ( secretory pathway ). Endo- and exocytosis describe vesicle budding and fusion at the plasma membrane and are by most authors not included in the term protein trafficking. Protein quality control comprize all cellular mechanisms, monitoring protein folding and detecting aberrant forms. 

Localized Calcium Microdomains Control Exocytosis of Glutamate in Astrocytes... 

Jourdain P, Bergersen LH, BhaukauraUy K, Bezzi P, Santello M, Domercq M, Matute C, Tonello F, Gundersen V, Volterra A (2007) Glutamate exocytosis from astrocytes controls synaptic strength. Nat Neurosci 10 331-339... 

Tse FW, Tse A, HiUe B, Horstmann H, Aimers W (1997) Local Ca + release from internal stores controls exocytosis in pituitary gonadotrophs. Neuron 18 121-132 Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M, Linden DJ, Worley PF (1998) Homer binds a novel proUne-rich motif and links group 1 metabotropic glutamate receptors with 1P3 receptors. Neuron 21 717-726... 

Vesicular compartment control over export, exocytosis, of enzymes, poisons... 

In summary, the release of nenrotransmitter from a presynaptic neurone into a synaptic cleft occurs via the process of exocytosis, which is regulated by the increase in Ca " ion concentration in the presynaptic terminal. The increase in Ca " ion concentration is achieved by release of Ca " ions by opening of the Ca ion channel in the endoplasmic reticulum, which is controlled by the concentration of IP3. Failure to release inositol from the inositol phosphates reduces the free inositol concentration, which interferes in the synthesis of PIP2. The phospholipase no longer catalyses a zero order reaction. Consequently, sufficient IP3 to activate the ion channel is released in the presynaptic neurone, so that less nenrotransmitter is released into the synaptic cleft (Figure 12.19). 

Figure 14.8 Simple diagram of release of neurotransmitter and recycling of the vesicles in presynaptic neurone. After exocytosis, the membrane recycles to form a new vesicle which is re-filled with neurotransmitter. The Ca ion binding protein may control packaging, formation of fusion pore and release of neurotransmitter.

Figure 14.13 The kinetic sequence of reactions that control the cyclic AMP concentration, and its binding to the effector system, and the kinetic sequence that controls the concentration of a neurotransmitter and its binding to the receptor on the postsyn-aptic membrane. Processes (1) are reactions catalysed by adenyl cyclase, and exocytosis. Reactions (2) are catalysed by phosphodiesterase and, for example, acetylcholinesterase. Reactions (3) are the interactions between the messenger and the effector system both the latter are equilibrium binding processes. (See Chapter 12 (p. 266) for discussions of equilibrium binding.)...

Selected entries from Methods in Enzymology [vol, page(s)] Chelation, 238, 74, 76, 297 buffers [for analysis of exocytosis, 221, 132 preparation, 219, 186 modulation of cytosolic buffering capacity with quin2, 221, 159] fluorescence assay, 240, 724-725, 740-742 fluorescence imaging, 225, 531 238, 303-304, 322-325, 334-335 free intracellular levels after bacterial invasion, 236, 482-489 free calcium in solutions for membrane fusion analysis, calculation and control, 221, 149 homeostasis mechanisms, 238, 80 hormonal elevation, 238, 79 inositol phosphate effect on release, 238, 207 determination of cytosolic levels [computer methods, 238, 73-75 with fura-2, 238, 73, 146 with indo-1, 238, 298, 316-317 with quin-2, 238, 297] hormone effects, 238, 79 ionomycin effects, 238, 79 membrane depolarization effects,... 

In Chapter 11 the effects of binding of hormones to cell surface receptors have been emphasized. Equally important are the mechanisms that control the secretion of hormones. The topic of exocytosis has been considered briefly in Chapter 8, Section C,6 and aspects of the Golgi in Fig. 20-8 and associated text. Both hormones and neurotransmitters are secreted by exocytosis of vesicles. Cells have two pathways for secretion.386 387 The constitutive pathway is utilized for continuous secretion of membrane constituents, enzymes, growth factors, viral proteins, and components of the extracellular matrix. This pathway carries small vesicles that originate in the trans-Golgi network (TGN Fig. 20-8). The regulated pathway is utilized for secretion of hormones and neurotransmitters in response to chemical, electrical, or other stimuli. 

A common feature, and also a puzzle, of vesicular signaling is the nearly universal response to calcium ions. Exocytosis is usually triggered by a rise in the concentration of Ca2+, and most receptor signaling also leads to an increase in cytosolic Ca2+.388-391 Tire puzzle lies in the ability of cells to use a common mechanism for so many specific purposes. This topic is considered further in Section B,8. There are also many other factors that can control exocytosis. Recent evidence suggests that NO may play a role.392... 

Details of the control of exocytosis are also uncertain. Synaptotagmin I, which contains two Ca2+-binding domains, is probably the sensor that detects the rapid influx of Ca2+ that initiates exocytosis.576 578b... 

Borisovska M, Zhao Y, Tsytsyura Y, Glyvuk N, Takamori S, Matti U, Rettig J, Siidhof T, Bruns D (2005) v-SNAREs control exocytosis of vesicles from priming to fusion. EMBO J. 24 2114-26 Bracher A, Weissenhorn W (2002) Structural basis for the Golgi membrane recruitment of Slylp by Sed5p. EMBO J 21 6114-24... 

Tang J, Maximov A, Shin OH, Dai H, Rizo J, Sudhof TC (2006) A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126 1175-87 Toonen RF, Verhage M (2003) Vesicle trafficking pleasure and pain from SM genes. Trends Cell Biol. 13 177-86... 

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