KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth

Fang Xu, Hironori Takahashi, Yosuke Tanaka, Sotaro Ichinose, Shinsuke Niwa, Matthew P. Wicklund, Nobutaka Hirokawa

Producción científica: Articlerevisión exhaustiva

21 Citas (Scopus)

Resumen

KIF1Bβ is a kinesin-3 family anterograde motor protein essential for neuronal development, viability, and function. KIF1Bβ 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 KIF1Bβ, and its binding and transport is specifically impaired by the Y1087C mutation of KIF1Bβ, 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 KIF1Bβ-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 KIF1Bβ in IGF1R transport, which may give new clue to the neuropathic pathogenesis.

Idioma originalEnglish (US)
Páginas (desde-hasta)3480-3496
Número de páginas17
PublicaciónJournal of Cell Biology
Volumen217
N.º10
DOI
EstadoPublished - oct 1 2018
Publicado de forma externa

ASJC Scopus subject areas

  • Cell Biology

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