Binding of alphaII spectrin to 14-3-3beta is involved in NCAM-dependent neurite outgrowth.
Members of the 14-3-3 protein family have been implicated in neuronal migration, synaptic plasticity and learning. Using affinity chromatography followed by mass spectrometry analysis, we show here that the cytoskeletal protein alphaII spectrin is a novel ligand of 14-3-3beta. We found that 14-3-3beta interacts with alphaII spectrin via the mode ... 2 14-3-3 binding motif RLIQS(1302)HP. Binding required phosphorylation of Ser(1302) by casein kinase II and was enhanced in the presence of calmodulin. Co-immunoprecipitation of alphaII spectrin and 14-3-3beta with the neural cell adhesion molecule NCAM suggested that the 14-3-3-spectrin-interaction affects NCAM function. Indeed, disruption of the 14-3-3beta/alphaII spectrin interaction by mutating Ser(1302) to Ala enhanced NCAM-dependent neurite outgrowth. Our results indicate that the phosphorylation-dependent interaction between 14-3-3beta and alphaII spectrin acts as a switch between positive and negative regulation of neurite outgrowth stimulated by NCAM, representing a novel and acute mechanism preventing uncontrolled elongation of neuronal processes.
Mesh Terms:
14-3-3 Proteins, Amino Acid Sequence, Animals, Brain, Calmodulin, Casein Kinase II, Cells, Cultured, Hippocampus, Humans, Neural Cell Adhesion Molecules, Neurites, Neurons, Protein Binding, Protein Isoforms, Rats, Recombinant Fusion Proteins, Spectrin
14-3-3 Proteins, Amino Acid Sequence, Animals, Brain, Calmodulin, Casein Kinase II, Cells, Cultured, Hippocampus, Humans, Neural Cell Adhesion Molecules, Neurites, Neurons, Protein Binding, Protein Isoforms, Rats, Recombinant Fusion Proteins, Spectrin
Mol. Cell. Neurosci.
Date: Sep. 01, 2010
PubMed ID: 20598904
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