| First Author | Xu F | Year | 2018 |
| Journal | J Cell Biol | Volume | 217 |
| Issue | 10 | Pages | 3480-3496 |
| PubMed ID | 30126838 | Mgi Jnum | J:265837 |
| Mgi Id | MGI:6201855 | Doi | 10.1083/jcb.201801085 |
| Citation | Xu F, et al. (2018) KIF1Bbeta mutations detected in hereditary neuropathy impair IGF1R transport and axon growth. J Cell Biol 217(10):3480-3496 |
| abstractText | KIF1Bbeta is a kinesin-3 family anterograde motor protein essential for neuronal development, viability, and function. KIF1Bbeta 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 KIF1Bbeta, and its binding and transport is specifically impaired by the Y1087C mutation of KIF1Bbeta, 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 KIF1Bbeta-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 KIF1Bbeta in IGF1R transport, which may give new clue to the neuropathic pathogenesis. |
