title: EphA4-dependent axon guidance is mediated by the RacGAP alpha2-chimaerin.
abstract: 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 alpha2-chimaerin binds activated EphA4 and mediates EphA4-triggered axonal growth cone collapse. alpha-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 alpha-chimaerin-dependent signaling pathway downstream of EphA4, which is essential for axon guidance decisions and neuronal circuit formation in vivo.
authors.affiliation: Department of Molecular Neurobiology and DFG Center for Molecular Physiology of the Brain, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Wegmeyer
authors.forename: Joaquim
authors.initials: J
authors.lastname: Egea
authors.forename: Nadine
authors.initials: N
authors.lastname: Rabe
authors.forename: Henrik
authors.initials: H
authors.lastname: Gezelius
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filosa
authors.forename: Anders
authors.initials: A
authors.lastname: Enjin
authors.forename: Frederique
authors.initials: F
authors.lastname: Varoqueaux
authors.forename: Katrin
authors.initials: K
authors.lastname: Deininger
authors.forename: Frank
authors.initials: F
authors.lastname: Schnütgen
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klein
authors.forename: Klas
authors.initials: K
authors.lastname: Kullander
authors.forename: Andrea
authors.initials: A
authors.lastname: Betz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism*; D020848:Chimerin 1 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D020233:Gait Disorders, Neurologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D011485:Protein Binding / Q000235:genetics; D011712:Pyramidal Tracts / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D036122:Receptor, EphA4 / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism