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

Cell. 2009 Nov 13;139(4):802-13. doi: 10.1016/j.cell.2009.10.023.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Growth Processes
  • Cell Line
  • Colon / cytology
  • Colon / embryology
  • Colon / innervation
  • Enteric Nervous System / embryology*
  • GRB2 Adaptor Protein / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Hirschsprung Disease / metabolism*
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neurons / metabolism
  • Proto-Oncogene Proteins c-ret / metabolism*
  • Signal Transduction*

Substances

  • GRB2 Adaptor Protein
  • Glial Cell Line-Derived Neurotrophic Factor
  • Proto-Oncogene Proteins c-ret
  • Ret protein, mouse
  • Kinesin

Associated data

  • GENBANK/GQ489027