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

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 st...

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Autores principales: Xu, Fang, Takahashi, Hironori, Tanaka, Yosuke, Ichinose, Sotaro, Niwa, Shinsuke, Wicklund, Matthew P., Hirokawa, Nobutaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168269/
https://www.ncbi.nlm.nih.gov/pubmed/30126838
http://dx.doi.org/10.1083/jcb.201801085
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author Xu, Fang
Takahashi, Hironori
Tanaka, Yosuke
Ichinose, Sotaro
Niwa, Shinsuke
Wicklund, Matthew P.
Hirokawa, Nobutaka
author_facet Xu, Fang
Takahashi, Hironori
Tanaka, Yosuke
Ichinose, Sotaro
Niwa, Shinsuke
Wicklund, Matthew P.
Hirokawa, Nobutaka
author_sort Xu, Fang
collection PubMed
description 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.
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spelling pubmed-61682692019-04-01 KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth Xu, Fang Takahashi, Hironori Tanaka, Yosuke Ichinose, Sotaro Niwa, Shinsuke Wicklund, Matthew P. Hirokawa, Nobutaka J Cell Biol Research Articles 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. Rockefeller University Press 2018-10-01 /pmc/articles/PMC6168269/ /pubmed/30126838 http://dx.doi.org/10.1083/jcb.201801085 Text en © 2018 Xu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Xu, Fang
Takahashi, Hironori
Tanaka, Yosuke
Ichinose, Sotaro
Niwa, Shinsuke
Wicklund, Matthew P.
Hirokawa, Nobutaka
KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
title KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
title_full KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
title_fullStr KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
title_full_unstemmed KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
title_short KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
title_sort kif1bβ mutations detected in hereditary neuropathy impair igf1r transport and axon growth
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168269/
https://www.ncbi.nlm.nih.gov/pubmed/30126838
http://dx.doi.org/10.1083/jcb.201801085
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