Synaptic proteins

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. 

Xiao, B., Tu, J. C., Petralia, R. S., et al. (1998) Homer regulates the association of group I metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins. Neuron 21,707-716. 

Lewy bodies (LB) are neuronal inclusions, composed of abnormal neurofilament and synaptic proteins, thought to be surrogate markers for neuronal dysfunction and eventual cell death. They are found in diverse locations including cholinergic and monoaminergic neurons of the brainstem, diencephalon. 

Levetiracetam Action on synaptic protein SV2A Well absorbed orally not bound to plasma proteins metabolized to 3 inactive metabolites ty2 6-11 h Generalized tonic-clonic seizures, partial seizures, generalized seizures Toxicity Nervousness, dizziness, depression, seizures Interactions Phenobarbital, phenytoin, carbamazepine, primidone... 

Short-term memory is not affected by inhibitors of protein synthesis, but alteration of synaptic proteins and membranes may be induced by covalent modification of existing macromolecules.1016 One way in which this happens has been described for Aplysia. As the snail learns a simple gill-withdrawal reflex, the duration of the action potentials in sensory neurons is increased, and there is a greater release of transmitters. This change comes about because stimulation of the sensory neuron causes simultaneous activation of... 

Siso S., Puig B., Varea R., Vidal E., Acin C., Prinz M., Montrasio F., Badiola J., Aguzzi A., Pumarola M., and Ferrer I. (2002). Abnormal synaptic protein expression and cell death in murine scrapie. ActaNeuropathol. (Berl) 103 615-626. 

The activity of N-type and P/Q-type calcium channels is also regulated by proteins that form part of the synaptic vesicle release machinery (Figure 3). These channel subtypes contain a specific synaptic protein interaction site (termed synprint) in the... 

It is worth noting that the binding interaction between synaptic proteins and GPy may allow G proteins to regulate synaptic activity independently of N-type channel activity. Taken together, the interactions between calcium channels, G proteins, kinases, and synaptic proteins such as syntaxin provide for complex mechanisms that regulate N-type calcium channel activity both in expression systems and in neurons. 

Harkins AB, Cahill AL, Powers JF, Tischler AS, Fox AP (2004) Deletion of the synaptic protein interaction site of the N-type (CaV2.2) calcium channel inhibits secretion in mouse pheochro-mocytoma cells. Proc Natl Acad Sci U S A 101 15219-24... 

Mochida S, Westenbroek RE, Yokoyama CT, Zhong H, Myers SJ, Scheuer T, Itoh K, CatteraU WA (2003) Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels. Proc Natl Acad Sci U S A 100 2819-24... 

Yokoyama CT, Myers SJ, Fu J, Mockus SM, Scheuer T, Catterall WA (2005) Mechanism of SNARE protein binding and regulation of Cav2 channels by phosphorylation of the synaptic protein interaction site. Mol Cell Neurosci 28 1-17 Yokoyama CT, Sheng ZH, Catterall WA (1997) Phosphorylation of the synaptic protein interaction site on N-type calcium channels inhibits interactions with SNARE proteins. J Neurosci 17 6929-38... 

Zamponi GW (2003) Regulation of presynaptic calcium channels by synaptic proteins. J Pharmacol Sci 92 79-83... 

Each neuron is a distinct anatomic unit, and no structural continuity exists between most neurons. Communication between nerve cells— and between nerve cells and effector organs—occurs through the release of specific chemical signals, called neurotransmitters, from the nerve terminals. This release depends on processes that are triggered by Ca++ uptake and regulated by phosphorylation of synaptic proteins. The neurotransmitters rapidly diffuse across the synaptic cleft or gap (synapse) between nerve endings and combine with specific receptors on the postsynaptic (target) cell (see pp. 37 and 57). 

Eastwood SL, Cotter D, Harrison PJ. 2001b. Cerebellar synaptic protein expression in schizophrenia. Neuroscience 105 ... 

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