|
KMID : 0624620080410120868
|
|
BMB Reports
2008 Volume.41 No. 12 p.868 ~ p.874
|
|
|
The effect of rod domain A148V mutation of neurofilament light chain on filament formation
|
|
Lee In-Bum
Kim Sung-Kuk
Chung Sang-Hee
Kim Ho
Kwon Taeg-Kyu
Min Do-Sik
Chang Jong-Soo
|
|
|
Abstract
|
|
|
|
Neurofilaments (NFs) are neuronal intermediate filaments composed of light (NF-L), middle (NF-M), and heavy (NF-H) subunits. NF-L self-assembles into a “core” filament with which NF-M or NF-H co-assembles to form the neuronal intermediate filament. Recent reports show that point mutations of the NF-L gene result in Charcot-Marie-Tooth disease (CMT). However, the most recently described rod domain mutant of human NF-L (A148V) has not been characterized in cellular level. We cloned human NF-L and used it to engineer the A148V. In phenotypic analysis using SW13 cells, A148V mutation completely abolished filament formation despite of presence of NF-M. Moreover, A148V mutation reduced the levels of in vitro self-assembly using GST-NF-L (H/R) fusion protein whereas control (A296T) mutant did not affect the filament formation. These results suggest that alanine at position 148 is essentially required for NF-L self-assembly leading to subsequent filament formation in neuronal cells.
|
|
|
KEYWORD
|
|
|
A148V, Charcot-marie-tooth, Neurofilaments, Self-assembly, SW13 cells
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|