Nck adaptor proteins control the organization of neuronal circuits important for walking

James P. Fawcett*, John Georgiou, Julie Ruston, Friedhelm Bladt, Andrew Sherman, Neil Warner, Bechara J. Saab, Rizaldy Scott, John C. Roder, Tony Pawson

*Corresponding author for this work

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

The intracellular signaling targets used by mammalian axon guidance receptors to organize the nervous system in vivo are unclear. The Nck1 and Nck2 SH2/SH3 adaptors (collectively Nck) can couple phosphotyrosine (pTyr) signals to reorganization of the actin cytoskeleton and are therefore candidates for linking guidance cues to the regulatory machinery of the cytoskeleton. We find that selective inactivation of Nck in the murine nervous system causes a hopping gait and a defect in the spinal central pattern generator, which is characterized by synchronous firing of bilateral ventral motor neurons. Nck-deficient mice also show abnormal projections of corticospinal tract axons and defective development of the posterior tract of the anterior commissure. These phenotypes are consistent with a role for Nck in signaling initiated by different classes of guidance receptors, including the EphA4 receptor tyrosine kinase. Our data indicate that Nck adaptors couple pTyr guidance signals to cytoskeletal events required for the ipsilateral projections of spinal cord neurons and thus for normal limb movement.

Original languageEnglish (US)
Pages (from-to)20973-20978
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number52
DOIs
StatePublished - Dec 26 2007

Keywords

  • Axon guidance
  • EphA4
  • Locomotion
  • SH2/SH3 adaptors

ASJC Scopus subject areas

  • General

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    Fawcett, J. P., Georgiou, J., Ruston, J., Bladt, F., Sherman, A., Warner, N., Saab, B. J., Scott, R., Roder, J. C., & Pawson, T. (2007). Nck adaptor proteins control the organization of neuronal circuits important for walking. Proceedings of the National Academy of Sciences of the United States of America, 104(52), 20973-20978. https://doi.org/10.1073/pnas.0710316105