Document Details

Document Type : Article In Journal 
Document Title :
Microtubule Destabilizer KIF2A Undergoes Distinct Site-Specific Phosphorylation Cascades that Differentially Affect Neuronal Morphogenesis.
Microtubule Destabilizer KIF2A Undergoes Distinct Site-Specific Phosphorylation Cascades that Differentially Affect Neuronal Morphogenesis.
 
Document Language : English 
Abstract : Neurons exhibit dynamic structural changes in response to extracellular stimuli. Microtubules (MTs) provide rapid and dramatic cytoskeletal changes within the structural framework. However, the molecular mechanisms and signaling networks underlying MT dynamics remain unknown. Here, we have applied a comprehensive and quantitative phospho-analysis of the MT destabilizer KIF2A to elucidate the regulatory mechanisms of MT dynamics within neurons in response to extracellular signals. Interestingly, we identified two different sets of KIF2A phosphorylation profiles that accelerate (A-type) and brake (B-type) the MT depolymerization activity of KIF2A. 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) induces 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. 
ISSN : 2211-1247 
Journal Name : Cell Rep 
Volume : 12 
Issue Number : 11 
Publishing Year : 1436 AH
2015 AD 
Article Type : Article 
Added Date : Tuesday, April 26, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Tadayuki OgawaOgawa, Tadayuki Investigator  
Nobutaka HirokawaHirokawa, Nobutaka Researcher hirokawa@m.u-tokyo.ac.jp

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