%0 Journal Article
%T KIF1B¦Â mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
%A Fang
%A Fang Xu
%A Hirokawa
%A Hironori
%A Hironori Takahashi
%A Ichinose
%A Matthew P.
%A Matthew P. Wicklund
%A Niwa
%A Nobutaka
%A Nobutaka Hirokawa
%A Shinsuke
%A Shinsuke Niwa
%A Sotaro
%A Sotaro Ichinose
%A Takahashi
%A Tanaka
%A Wicklund
%A Xu
%A Yosuke
%A Yosuke Tanaka
%J JCB | The Journal of Cell Biology
%D 2018
%R 10.1083/jcb.201801085
%X KIF1B¦Â is a kinesin-3 family anterograde motor protein essential for neuronal development, viability, and function. KIF1B¦Â mutations have previously been reported in a limited number of pedigrees of Charcot-Marie-Tooth disease type 2A (CMT2A) neuropathy. However, the gene responsible for CMT2A is still controversial, and the mechanism of pathogenesis remains elusive. In this study, we show that the receptor tyrosine kinase IGF1R is a new direct binding partner of KIF1B¦Â, and its binding and transport is specifically impaired by the Y1087C mutation of KIF1B¦Â, which we detected in hereditary neuropathic patients. The axonal outgrowth and IGF-I signaling of Kif1b£¿/£¿ neurons were significantly impaired, consistent with decreased surface IGF1R expression. The complementary capacity of KIF1B¦Â-Y1087C of these phenotypes was significantly impaired, but the binding capacity to synaptic vesicle precursors was not affected. These data have supported the relevance of KIF1B¦Â in IGF1R transport, which may give new clue to the neuropathic pathogenesis.
%U http://jcb.rupress.org/content/217/10/3480