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Nck adaptor proteins control the organization of neuronal circuits important for walking.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2007 Dec 26; Vol. 104 (52), pp. 20973-8. Date of Electronic Publication: 2007 Dec 18. - Publication Year :
- 2007
-
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.
- Subjects :
- Actins chemistry
Adaptor Proteins, Signal Transducing
Animals
Axons metabolism
Chimerin 1 metabolism
Cytoskeleton metabolism
Fibroblasts metabolism
Locomotion
Mice
Models, Biological
Motor Neurons metabolism
Oncogene Proteins metabolism
Phenotype
Receptor, EphA4 chemistry
Signal Transduction
Spinal Cord metabolism
src Homology Domains
Oncogene Proteins physiology
Walking
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 104
- Issue :
- 52
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 18093944
- Full Text :
- https://doi.org/10.1073/pnas.0710316105