EphA4-Dependent Axon Guidance Is Mediated by the RacGAP α2-Chimaerin
2007 (English)In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 55, no 5, 756-767 p.Article in journal (Refereed) Published
Neuronal network formation in the developing nervous system is dependent on the accurate navigation of nerve cell axons and dendrites, which is controlled by attractive and repulsive guidance cues. Ephrins and their cognate Eph receptors mediate many repulsive axonal guidance decisions by intercellular interactions resulting in growth cone collapse and axon retraction of the Eph-presenting neuron. We show that the Rac-specific GTPase-activating protein α2-chimaerin binds activated EphA4 and mediates EphA4-triggered axonal growth cone collapse. α-Chimaerin mutant mice display a phenotype similar to that of EphA4 mutant mice, including aberrant midline axon guidance and defective spinal cord central pattern generator activity. Our results reveal an α-chimaerin-dependent signaling pathway downstream of EphA4, which is essential for axon guidance decisions and neuronal circuit formation in vivo.
Place, publisher, year, edition, pages
2007. Vol. 55, no 5, 756-767 p.
Animals, Animals; Newborn, Brain/abnormalities/metabolism/physiopathology, Cell Communication/genetics, Cell Differentiation/*genetics, Cells; Cultured, Central Nervous System/*abnormalities/cytology/*metabolism, Chimerin 1/genetics/*metabolism, Down-Regulation/genetics, Gait Disorders; Neurologic/genetics/metabolism/physiopathology, Gene Expression Regulation; Developmental/genetics, Growth Cones/*metabolism/ultrastructure, Mice, Mice; Knockout, Neural Pathways/abnormalities/metabolism/physiopathology, Protein Binding/genetics, Pyramidal Tracts/abnormalities/metabolism/physiopathology, Receptor; EphA4/*metabolism, Signal Transduction/genetics, Spinal Cord/abnormalities/cytology/metabolism
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-14467DOI: 10.1016/j.neuron.2007.07.038ISI: 000249857000011PubMedID: 17785182OAI: oai:DiVA.org:uu-14467DiVA: diva2:42237