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cover story(Frontiers in Biology, 2012 issue 5)

已有 3074 次阅读 2012-9-26 10:12 |系统分类:论文交流| 2012, cover

Cover Story  

Neurons communicate with each other via specialized inter-cellular junctions called synapses shown in the cover illustration. Excitatory synapses are characterized by an enrichment of presynaptic vesicles at the axon terminal and postsynaptic electron-dense membrane thickenings (referred to as postsynaptic density, PSD) at the top of dendritic spines. Upon stimulation, neurotransmitters are released from the presynaptic terminal and act on the specific receptors on the postsynaptic side to initiate signaling processes. Thus, neuronal signals are received, decoded and further propagated via the PSD, which is a mega membrane-associated organelle specialized for postsynaptic signal transduction and processing. PSD is composed of thousands of densely packed proteins including membrane receptors; cell-adhesion molecules; enzymes and their regulators; scaffold proteins; cytoskeleton elements; membrane trafficking proteins and molecular motors; protein synthesis machineries; etc. The architecture of the PSD is highly dynamic, not only during developmental processes, but also in response to synaptic activity.

Scaffold proteins are abundant components of the PSD and known to play critical roles in very diverse PSD functions, including trafficking, anchoring and clustering of ion channels/receptors; linking receptors with their downstream signaling proteins; organizing multiple components into very large signaling complexes; interfacing with and regulating the dynamics of cytoskeletal structures. Membrane-associated guanylate kinases (MAGUKs) are among the earliest identified and the most abundant scaffold proteins in synapses. MAGUKs play essential roles in tissue developments, cell-cell communications, cell polarity control, and cellular signal transductions. Genetic mutations of MAGUKs are known to cause various brain disorders including X-linked mental retardations and autism spectrum disorder. In a review in this issue, Zhu et al. (pages 379-396) summarize the structural basis governing cellular function of various members of the MAGUKs. They also describe their very recent discoveries of MAGUK guanylate kinase domains as specific phospho-protein interaction modules, and discuss functional implications and connections to human diseases of such regulated MAGUK guanylate kinase/target interactions.  (Image illustration by Wensi Sheng at the Blot Media Limited)

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