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Studies from University of Colorado, Medical Department yield new information about tissue engineering
2009 AUG 24 - (NewsRx.com) -- "A-kinase anchoring protein (AKAP) 79/150 is a scaffold protein found in dendritic spines that recruits the cAMP-dependent protein kinase (PKA) and protein phosphatase 2B-calcineurin (CaN) to membrane-associated guanylate kinase (MAGUK)-linked AMPA receptors (AMPARs) to control receptor phosphorylation and synaptic plasticity. However, AKAP79/150 may also coordinate regulation of AMPAR activity with spine structure directly through MAGUK binding and membrane-cytoskeletal interactions of its N-terminal targeting domain," scientists in the United States report. "In cultured hippocampal neurons, we observed that rat AKAP150 expression was low early in development but then increased coincident with spine formation and maturation. Overexpression of human AKAP79 in immature or mature neurons increased the number of dendritic filopodia and spines and enlarged spine area. However, RNA interference knockdown of AKAP150 decreased dendritic spine area only in mature neurons. Importantly, AKAP79 overexpression in immature neurons increased AMPAR postsynaptic localization and activity. Neither the AKAP79 PKA nor CaN anchoring domain was required for increasing dendritic protrusion numbers, spine area, or AMPAR synaptic localization; however, an internal region identified as the MAGUK binding domain was found to be essential as shown by expression of a MAGUK binding mutant that formed mainly filopodia and decreased AMPAR synaptic localization and activity. Expression of the AKAP79 N-terminal targeting domain alone also increased filopodia numbers but not spine area," wrote H.R. Robertson and colleagues, University of Colorado, Medical Department. The researchers concluded: "Overall, these results demonstrate a novel structural role for AKAP79/150 in which the N-terminal targeting domain induces dendritic filopodia and binding to MAGUKs promotes spine enlargement and AMPAR recruitment.." Robertson and colleagues published their study in the Journal of Neuroscience (Regulation of Postsynaptic Structure and Function by an A-Kinase Anchoring Protein-Membrane-Associated Guanylate Kinase Scaffolding Complex. Journal of Neuroscience, 2009;29(24):7929-7943). For more information, contact H.R. Robertson, University of Colorado Denver, School Medical, Dept. of Pharmacology, Anschutz Med Campus, Mail Stop 8303, 12800 E 19th A, Aurora, CO 80045, USA. Publisher contact information for the Journal of Neuroscience is: Society Neuroscience, 11 Dupont Circle, NW, Ste. 500, Washington, DC 20036, USA. Keywords: United States, Aurora, Enzyme Research, Kinase, Neuroscience, Phosphatase, Tissue Engineering, University of Colorado, Medical Department. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
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