KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development.
basic_science · Level V
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- Record sourced from PubMed, PMID 19914172.
- Also identified by DOI 10.1016/j.cell.2009.10.023.
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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.
Medical subject headings
- Enteric Nervous System
- Glial Cell Line-Derived Neurotrophic Factor
- Hirschsprung Disease
- Kinesins
- Proto-Oncogene Proteins c-ret
- Signal Transduction