| First Author | Fell SM | Year | 2017 |
| Journal | Genes Dev | Volume | 31 |
| Issue | 10 | Pages | 1036-1053 |
| PubMed ID | 28637693 | Mgi Jnum | J:245948 |
| Mgi Id | MGI:5914275 | Doi | 10.1101/gad.297077.117 |
| Citation | Fell SM, et al. (2017) Neuroblast differentiation during development and in neuroblastoma requires KIF1Bbeta-mediated transport of TRKA. Genes Dev 31(10):1036-1053 |
| abstractText | We recently identified pathogenic KIF1Bbeta mutations in sympathetic nervous system malignancies that are defective in developmental apoptosis. Here we deleted KIF1Bbeta in the mouse sympathetic nervous system and observed impaired sympathetic nervous function and misexpression of genes required for sympathoadrenal lineage differentiation. We discovered that KIF1Bbeta is required for nerve growth factor (NGF)-dependent neuronal differentiation through anterograde transport of the NGF receptor TRKA. Moreover, pathogenic KIF1Bbeta mutations identified in neuroblastoma impair TRKA transport. Expression of neuronal differentiation markers is ablated in both KIF1Bbeta-deficient mouse neuroblasts and human neuroblastomas that lack KIF1Bbeta. Transcriptomic analyses show that unfavorable neuroblastomas resemble mouse sympathetic neuroblasts lacking KIF1Bbeta independent of MYCN amplification and the loss of genes neighboring KIF1B on chromosome 1p36. Thus, defective precursor cell differentiation, a common trait of aggressive childhood malignancies, is a pathogenic effect of KIF1Bbeta loss in neuroblastomas. Furthermore, neuropathy-associated KIF1Bbeta mutations impede cargo transport, providing a direct link between neuroblastomas and neurodegeneration. |
