Active zones

The sense of this procedure may be verified in Figure 4.13. An implicit assumption in this procedure is that the speed at which the sources are activated equals the speed at which the activation zone is propagated. This holds only if the flame propagates into a quiescent mixture, which does not really happen. Computational experiments with the proposed model show that this assumption is increasingly justified as a cloud s aspect ratio increases. 

Membrane-bound GTP rabs recruit effectors to the membrane. In neurons and neuroendocrine cells, the vesicle-associated Rab3 binds to rabphilin and to RIM. RIM is a component of the presynaptic cytomatrix and may thus serve as a docking receptor for synaptic vesicles at the active zone. 

Although several metals, such as Pt and Ag, can also act as electrocatalysts for reaction (3.7) the most efficient electrocatalysts known so far are perovskites such as Lai-xSrxMn03. These materials are mixed conductors, i.e., they exhibit both anionic (O2 ) and electronic conductivity. This, in principle, can extend the electrocatalytically active zone to include not only the three-phase-boundaries but also the entire gas-exposed electrode surface. 

Figure 4.11 Dephosphorylated synapsin, associated with SSVs, is thought to form a heteromeric complex with CAM kinase II (also partially embedded in the vesicular membrane) and actin filaments. An increase in intracellular Ca + triggers phosphorylation of S3mapsin I which dissociates from the vesicular membrane. This frees the vesicles from the fibrin microfilaments and makes them available for transmitter release at the active zone of the nerve terminal...

Taking ai-adrenoceptors as an example, several possible mechanisms have been suggested (see Starke 1987). The first rests on evidence that these autoreceptors are coupled to a Gi (like) protein so that binding of an a2-adrenoceptor agonist to the receptor inhibits the activity of adenylyl cyclase. This leads to a fall in the synthesis of the second messenger, cAMP, which is known to be a vital factor in many processes involved in exocytosis. In this way, activation of presynaptic a2-adrenoceptors could well affect processes ranging from the docking of vesicles at the active zone to the actual release process itself... 

Feed concentration Active zone concentration Deadzone concentration Effluent concentration Ideal tank concentration Total flow rate Fractional by-pass flow By-pass flow rate Dead volume fraction Deadzone exchange flow Rate constant Fractional conversion Fractional deadzone flow... 

Yao I, Takagi H, Ageta H, et al. SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell 2007 130 943-957. 

Those vesicles have been primed by docking at the active zone and are therefore ready for exocytosis upon arrival of an action potential. However, for the synapse to respond rapidly and repeatedly under heavy physiological demand, these exocytosed vesicles must be rapidly replaced. This is accomplished first from the recycled pool of vesicles and, as the demand increases, from the reserve pool. To be recycled, synaptic vesicles must be reloaded quickly after they release their contents. The sequence of events that is triggered by neurotransmitter exocytosis is known as the synaptic vesicle cycle [73,74] (Fig. 9-8). 

Neurexins a protein kinase. A component of active zones that interact with RIM, syntaxin and other proteins. Cell surface proteins with more than 1,000 isoforms generated by alternative splicing from three genes. Neurexins include one of the receptors for aratrotoxin and may function in cell-cell recognition between neurons. 

Voltage-gated Ca2+ channels Mediate Ca2+ influx for neurotransmitter release at the active zone. 

In the classic model of synaptic vesicle recycling in nerve terminals, synaptic vesicles fuse completely with the plasma membrane and the integrated vesicle proteins move away from the active zone to adjacent membrane regions (Fig. 9-9A). In these regions, clathrin-mediated synaptic vesicle endocytosis takes place rapidly after neurotransmitter release (within seconds) [64]. The process starts with the formation of a clathrin-coated pit that invaginates toward the interior of the cell and pinches off to form a clathrin-coated vesicle [83]. Coated vesicles are transient organelles that rapidly shed their coats in an ATP/chaperone dependent process. Once uncoated, the recycled vesicle fuses with a local EE for reconstitution as a synaptic vesicle. Subsequently, the recycled synaptic vesicle is filled with neurotransmitter and it returns to the release site ready for use. This may be the normal pathway when neurotransmitter release rates are modest. Clathrin/ EE-based pathways become essential when synaptic proteins have been incorporated into the presynaptic plasma membrane. 

Powell, C. M., Schoch, S., Monteggia, L. et al. The presynaptic active zone protein RIMla is critical for normal learning and memory. Neuron 42 143-153,2004. 

FIGURE 43-2 Photomicrograph of the human neuromuscular junction. In normal muscle, Ach receptors are associated with the terminal expansions of the junctional folds and the architecture of the postjunctional membrane follows closely the distribution of active zones in the presynaptic membrane, b, basal lamina I, infoldings m, mitochondria M, myocyte N, nerve terminal r, ribosomes s, synaptic space S, Schwann cell. Courtesy of A. Engel. 

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