The University of Tokyo Global COE Integrative Life Science Based on the Study of Biosignaling Mechanisms
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A novel kinesin superfamily protein that controls GDNF-Ret signaling in enteric neuronal development

(Zhou R., Niwa S., Homma N., Takei Y., Hirokawa N. (2009). KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development. Cell 139, 802-813.)

Enteric nervous system (ENS) is essential for peristalsis. But molecular mechanism of ENS development is not completely understood. Hirokawa group newly identified KIF26A and found that mice with a homozygous deletion of kif26a developed a megacolon with enteric nerve hyperplasia. Kif26a -/- enteric neurons showed hypersensitivity for GDNF-Ret signaling, and KIF26A suppressed GDNF-Ret signaling by direct binding and inhibition of Grb2, an essential component of GDNF/Akt/ERK signaling. Taken together, it was revealed the unconventional kinesin KIF26A plays a key role in enteric nervous system development by repressing a cell growth signaling pathway.

Program member
Nobutaka Hirokawa (Department of Cell Biology and Anatomy, Graduate School of Medicine)

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Figure 1 kif26a-/- mice developed a megacolon

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Figure 2 KIF26A regulates GDNF-Ret signaling by binding with GRB2