The architecture of an excitatory synapse
Chua JJ, Kindler S, Boyken J, Jahn R.
The functioning of excitatory synapses in the mammalian brain is governed by macromolecular complexes that are held together by protein-protein, protein-lipid and lipid-lipid interactions. On the presynaptic side, neurotransmitter (NT)-filled synaptic vesicles (SVs) are recruited to specialized release sites termed active zones. Glutamate is the major excitatory NT. It is released from presynaptic boutons, diffuses across the synaptic cleft and binds to postsynaptic NT receptors that alter the membrane potential and trigger signal transduction cascades. Action potentials arriving at presynaptic boutons trigger exocytosis and the retrieval of SV components from presynaptic membranes after membrane fusion (Jin and Garner, 2008; Schoch and Gundelfinger, 2006; Sudhof, 2004). On the postsynaptic side, multiprotein complexes that ake up a region known as the postsynaptic density (PSD) mediate clustering of receptors and cell-adhesion molecules (CAMs) and orchestrate the coupling of diverse signaling components (Kim and Sheng, 2004). It has emerged that the loss or dysregulation of many synaptic proteins is a cause of a variety of neurological diseases. In this article, we describe the steps involved in synaptic transmission at excitatory central nervous system synapses and give an overview of the proteins governing these steps. To assist in orientation, the stages of the synaptic vesicle recycling pathway are numbered in the accompanying poster and are referred to in sequence below.
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