KIF26A Is an Unconventional Kinesin and Regulates GDNF-Ret Signaling in Enteric Neuronal Development

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

doi:10.1016/j.cell.2009.10.023

KIF26A Is an Unconventional Kinesin and Regulates GDNF-Ret Signaling in Enteric Neuronal Development

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

Advanced Interdisciplinary Research Division

Research output: Contribution to journal › Article › peer-review

70 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	802-813
Number of pages	12
Journal	Cell
Volume	139
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2009.10.023
Publication status	Published - 2009 Nov 13

Keywords

CELLBIO
MOLNEURO
SIGNALING

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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@article{d296b4bcf0d2434db2fd2e0d91e0bb03,

title = "KIF26A Is an Unconventional Kinesin and Regulates GDNF-Ret Signaling in Enteric Neuronal Development",

abstract = "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.",

keywords = "CELLBIO, MOLNEURO, SIGNALING",

author = "Ruyun Zhou and Shinsuke Niwa and Noriko Homma and Yosuke Takei and Nobutaka Hirokawa",

note = "Funding Information: We thank A. Miyajima (University of Tokyo) for GST-RBD, J. Miyazaki (Osaka University) for the CAG-Cre mice, Kazusa DNA Research Institute for the KIAA1236 clone, and L.E. Samelson (National Institutes of Health) for Grb2 cDNA. We also thank Y. Tanaka, K. Nakajima, R. Nitta, and H. Ueno for their supervision and discussion, H. Sato, H. Fukuda, M. Sugaya, N. Onouchi, T. Akamatsu, and T. Aizawa for their technical assistance, and all other members of the Hirokawa laboratory for their help and discussion. This work was supported by a grant in aid for specially promoted research to N.H. and also by a Global COE Program from the Ministry of Education, Science, Sports, and Culture of Japan. ",

year = "2009",

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language = "English",

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T1 - KIF26A Is an Unconventional Kinesin and Regulates GDNF-Ret Signaling in Enteric Neuronal Development

AU - Zhou, Ruyun

AU - Niwa, Shinsuke

AU - Homma, Noriko

AU - Takei, Yosuke

AU - Hirokawa, Nobutaka

N1 - Funding Information: We thank A. Miyajima (University of Tokyo) for GST-RBD, J. Miyazaki (Osaka University) for the CAG-Cre mice, Kazusa DNA Research Institute for the KIAA1236 clone, and L.E. Samelson (National Institutes of Health) for Grb2 cDNA. We also thank Y. Tanaka, K. Nakajima, R. Nitta, and H. Ueno for their supervision and discussion, H. Sato, H. Fukuda, M. Sugaya, N. Onouchi, T. Akamatsu, and T. Aizawa for their technical assistance, and all other members of the Hirokawa laboratory for their help and discussion. This work was supported by a grant in aid for specially promoted research to N.H. and also by a Global COE Program from the Ministry of Education, Science, Sports, and Culture of Japan.

PY - 2009/11/13

Y1 - 2009/11/13

N2 - 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.

AB - 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.

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