KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development.
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.
Zhou
Ruyun
R
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Niwa
Shinsuke
S
Homma
Noriko
N
Takei
Yosuke
Y
Hirokawa
Nobutaka
N
D000818:Animals; D048708:Cell Growth Processes; D002460:Cell Line; D003106:Colon / Q000166:cytology / Q000196:embryology / Q000294:innervation; D017615:Enteric Nervous System / Q000196:embryology*; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006627:Hirschsprung Disease / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D015398:Signal Transduction
D051380:GRB2 Adaptor Protein; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse; D016547:Kinesins