Quantitative mapping of microtubule-associated protein 2c (MAP2c) phosphorylation and regulatory protein 14-3-3ζ-binding sites reveals key differences between MAP2c and its homolog Tau.

摘要: Microtubule-associated protein 2c (MAP2c) is involved in neuronal development and less characterized than its homolog Tau, which has various roles neurodegeneration. Using NMR methods providing single-residue resolution quantitative comparison, we investigated molecular interactions important for the regulatory of MAP2c microtubule dynamics. We found that Tau significantly differ position kinetics sites are phosphorylated by cAMP-dependent kinase (PKA), even highly homologous regions. determined binding unphosphorylated responsible with 14-3-3ζ. Differences phosphorylation charge distribution between suggested both respond to same signal (phosphorylation PKA) but have different downstream effects, indicating a signaling branch point controlling stability. Although 14-3-3ζ supposed be major factor destabilization, enhanced PKA-mediated likely influence microtubule-MAP2c much less, agreement results our tubulin co-sedimentation measurements. The specific location site region muscarinic receptor-binding suggests also may regulate processes other