KIF26A Is an Unconventional Kinesin and Regulates GDNF-Ret Signaling in Enteric Neuronal Development
KIF26A Is an Unconventional Kinesin and Regulates GDNF-Ret Signaling in Enteric Neuronal Development
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DOI：
10.1016/j.cell.2009.10.023
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发表时间：
2009-11-13
期刊：
影响因子：
64.5
通讯作者：
Hirokawa, Nobutaka
中科院分区：
文献类型：
--
作者：
Zhou, Ruyun;Niwa, Shinsuke;Hirokawa, Nobutaka
驱动蛋白超家族蛋白（KIFs）是以微管和ATP依赖的方式运输细胞器和蛋白质复合物的马达蛋白。我们将KIF26A鉴定为鼠KIFs的新成员。KIF26A是一个相当不典型的成员，因为它缺乏ATP酶活性。具有Kif26a纯合缺失的小鼠发展为具有肠神经增生的巨结肠。Kif26a（-/-）肠神经元表现出对GDNF-Ret信号的超敏反应，我们发现KIF26A通过直接结合和抑制GDNF/Akt/ERK信号的重要组成部分Grb 2来抑制GDNF-Ret信号。因此，我们认为非常规驱动蛋白KIF26A通过抑制细胞生长信号通路在肠神经系统发育中起着关键作用。
The kinesin superfamily proteins (KIFs) are motor proteins that transport organelles and protein complexes in a microtubule- and ATP-dependent manner. We identified KIF26A as a new member of the murine KIFs. KIF26A is a rather atypical member as it lacks ATPase activity. Mice with a homozygous deletion of Kif26a developed a megacolon with enteric nerve hyperplasia. Kif26a(-/-) enteric neurons showed hypersensitivity for GDNF-Ret signaling, and we find that KIF26A suppressed GDNF-Ret signaling by direct binding and inhibition of Grb2, an essential component of GDNF/Akt/ERK signaling. We therefore propose that the unconventional kinesin KIF26A plays a key role in enteric nervous system development by repressing a cell growth signaling pathway.