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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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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. |
format | Online Article Text |
id | pubmed-6168269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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