1B-W1-1735 PDF
Toward a Thorough Understanding of the Dynamic Behavior of the Key Molecule in Neuron
In basic biological research, it is crucial to identify the dynamic changes in the target molecules and quantify their behavior under diverse conditions. In this presentation, we will introduce the systematic approaches to transform the conventional qualitative analysis into systematic, quantitative, targeted analyses. We will also discuss about the success stories thorough lots of failures and pitfalls in mass spectrometry-based biological analyses. We believe these strategic approaches are promising for understanding target molecules from quantitative perspectives.
In neurons, microtubules (MTs) provide rapid and dramatic cytoskeletal changes in response to extracellular stimuli. We have applied MS-based analyses of the MT destabilizer KIF2A to elucidate the regulatory mechanisms of MT dynamics within neurons. We identified two different sets of phosphorylation profiles of KIF2A that accelerate (A-type) and brake (B-type) the MT depolymerization activity of KIF2A, respectively. Brain-derived neurotrophic factor (BDNF) stimulates PAK1 and CDK5 kinases, which decrease the MT depolymerizing activity of KIF2A through B-type phosphorylation, resulting in enhanced outgrowth of neural processes. In contrast, lysophosphatidic acid (LPA) induced ROCK2 kinase, which suppresses neurite outgrowth from round cells via A-type phosphorylation. We propose that these two mutually exclusive forms of KIF2A phosphorylation differentially regulate neuronal morphogenesis during development.