Document Details

Document Type : Article In Journal 
Document Title :
β‐Tubulin mutations that cause severe neuropathies disrupt axonal transport
β‐Tubulin mutations that cause severe neuropathies disrupt axonal transport
 
Document Language : English 
Abstract : Microtubules are fundamental to neuronal morphogenesis and function. Mutations in tubulin, the major constituent of microtubules, result in neuronal diseases. Here, we have analysed β-tubulin mutations that cause neuronal diseases and we have identified mutations that strongly inhibit axonal transport of vesicles and mitochondria. These mutations are in the H12 helix of β-tubulin and change the negative charge on the surface of the microtubule. This surface is the interface between microtubules and kinesin superfamily motor proteins (KIF). The binding of axonal transport KIFs to microtubules is dominant negatively disrupted by these mutations, which alters the localization of KIFs in neurons and inhibits axon elongation in vivo. In humans, these mutations induce broad neurological symptoms, such as loss of axons in the central nervous system and peripheral neuropathy. Thus, our data identified the critical region of β-tubulin required for axonal transport and suggest a molecular mechanism for human neuronal diseases caused by tubulin mutations. 
ISSN : 0261-4189 
Journal Name : The EMBO journal 
Volume : 32 
Issue Number : 10 
Publishing Year : 1434 AH
2013 AD 
Article Type : Article 
Added Date : Thursday, March 10, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Shinsuke NiwaNiwa, Shinsuke Investigator  
Hironori TakahashiTakahashi, Hironori Researcher  
Nobutaka HirokawaHirokawa, Nobutaka Researcher  

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