Scaffold Proteins at the Postsynaptic Density
Scaffold proteins are abundant and essential components of the postsynaptic density (PSD). They play a major role in many synaptic functions including the trafficking, anchoring, and clustering of glutamate receptors and adhesion molecules. Moreover, they
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Scaffold Proteins at the Postsynaptic Density Chiara Verpelli, Michael J. Schmeisser, Carlo Sala, and Tobias M. Boeckers
Abstract Scaffold proteins are abundant and essential components of the postsynaptic density (PSD). They play a major role in many synaptic functions including the trafficking, anchoring, and clustering of glutamate receptors and adhesion molecules. Moreover, they link postsynaptic receptors with their downstream signaling proteins and regulate the dynamics of cytoskeletal structures. By definition, PSD scaffold proteins do not have intrinsic enzymatic activities but are formed by modular and specific domains deputed to form large protein networks. Here, we will discuss the latest findings regarding the structure and functions of major PSD scaffold proteins. Given that scaffold proteins are central components of PSD architecture, it is not surprising that deletion or mutations in their human genes cause severe neuropsychiatric disorders including autism, mental retardation, and schizophrenia. Thus, their dynamic organization and regulation are directly correlated with the essential structure of the PSD and the normal physiology of neuronal synapses. Keywords BMP signaling • Development • Glutamate receptors • Neuromuscular junction • Wnt signaling
C. Verpelli • C. Sala (*) CNR Institute of Neuroscience, Department of Pharmacology, University of Milan and Neuromuscular Diseases and Neuroimmunology, Neurological Institute Foundation Carlo Besta, Via Vanvitelli 32, 20129 Milan, Italy e-mail: [email protected] M.J. Schmeisser • T.M. Boeckers (*) Institute of Anatomy and Cell Biology, Ulm University Faculty of Medicine, Albert Einstein Allee 11, 89081 Ulm, Germany e-mail: [email protected] M.R. Kreutz and C. Sala (eds.), Synaptic Plasticity, Advances in Experimental Medicine and Biology 970, DOI 10.1007/978-3-7091-0932-8_2, # Springer-Verlag/Wien 2012
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The MAGUK Family Structural Organization of the MAGUK Proteins
Genetic and biochemical studies over the past 20 years have identified the membrane-associated guanylate kinases (MAGUKs) as ubiquitous scaffolding molecules concentrated at sites of cell-cell contact such as synapses (Craven and Bredt 1998; Kornau et al. 1997; Sheng and Sala 2001; Sheng and Kim 2002). MAGUK members include SAP90/PSD-95, SAP102, SAP97, Chapsyn 110/ PSD93, and p55 (SAP ¼ synapse-associated protein). They represent a superfamily of multidomain proteins that are related by the presence of a shared set of structural domains. The defining feature of MAGUKs is the presence of a region of approximately 300 amino acids at the C-terminus with homology to yeast guanylate kinase (GK), which catalyzes the ATP-dependent phosphorylation of GMP to GDP. Curiously, the GK domain in MAGUKs is catalytically inactive (Olsen and Bredt 2003), but it is always accompanied by either a preceding SH3 (Src homology 3) domain or followed closely by a WW (two conserved Trp residues) motif. Also, MAGUKs always contain PDZ (PSD-95/DLG/ZO-1) domains (in most
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