Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta.
Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta.
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发表时间：
2001
期刊：
影响因子：
64.5
通讯作者：
C. Zhao;J. Takita;Y. Tanaka;M. Setou;T. Nakagawa;S. Takeda;H. W. Yang;S. Terada;T. Nakata;Y. Takei;M. Saito;S. Tsuji;Y. Hayashi;N. Hirokawa
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作者：
C. Zhao;J. Takita;Y. Tanaka;M. Setou;T. Nakagawa;S. Takeda;H. W. Yang;S. Terada;T. Nakata;Y. Takei;M. Saito;S. Tsuji;Y. Hayashi;N. Hirokawa
驱动蛋白超家族马达蛋白KIF 1B已被证明转运线粒体。在这里，我们描述了KIF 1B，KIF 1Bbeta，这是从KIF 1B在其货物结合域不同的同种型。KIF 1B基因敲除小鼠在出生时死于神经系统缺陷引起的呼吸暂停。通过表达β同种型可以挽救培养物中敲除神经元的死亡。KIF 1B杂合子在运输突触囊泡前体方面有缺陷，并患有类似于人类神经病的进行性肌无力。Charcot-Marie-Tooth病2A型以前被映射到含有KIF 1B的间隔。我们发现CMT 2A患者在KIF 1B基因的运动域中含有功能缺失突变。这清楚地表明，由于突变的运动蛋白引起的轴突运输缺陷可能是人类周围神经病变的基础。
The kinesin superfamily motor protein KIF1B has been shown to transport mitochondria. Here, we describe an isoform of KIF1B, KIF1Bbeta, that is distinct from KIF1B in its cargo binding domain. KIF1B knockout mice die at birth from apnea due to nervous system defects. Death of knockout neurons in culture can be rescued by expression of the beta isoform. The KIF1B heterozygotes have a defect in transporting synaptic vesicle precursors and suffer from progressive muscle weakness similar to human neuropathies. Charcot-Marie-Tooth disease type 2A was previously mapped to an interval containing KIF1B. We show that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene. This is clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy.