KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development.

Ruyun Zhou, Shinsuke Niwa, Noriko Homma, Yosuke Takei, Nobutaka Hirokawa

Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

Cell 2009 Nov 13

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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.

Citation

Ruyun Zhou, Shinsuke Niwa, Noriko Homma, Yosuke Takei, Nobutaka Hirokawa. KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development. Cell. 2009 Nov 13;139(4):802-13