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alpha2-Chimaerin is an essential EphA4 effector in the assembly of neuronal locomotor circuits
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 156896
Author(s) Beg, Asim A; Sommer, Julia E; Martin, John H; Scheiffele, Peter
Author(s) at UniBasel Scheiffele, Peter
Year 2007
Title alpha2-Chimaerin is an essential EphA4 effector in the assembly of neuronal locomotor circuits
Journal Neuron
Volume 55
Number 5
Pages / Article-Number 768-78
Keywords Animals; Cell Communication/genetics; Cell Differentiation/genetics; Central Nervous System/*abnormalities/*metabolism/physiopathology; Cerebral Cortex/abnormalities/metabolism/physiopathology; Chimerin 1/genetics/metabolism/*physiology; Gait Disorders; Neurologic/genetics/metabolism/physiopathology; Gene Expression Regulation; Developmental/genetics; Growth Cones/metabolism/ultrastructure; Hindlimb/innervation/physiopathology; Mice; Mutant Strains; Neural Pathways/*abnormalities/*metabolism/physiopathology; Phenotype; Pyramidal Tracts/abnormalities/metabolism/physiopathology; Receptor; EphA4/*metabolism; Spinal Cord/abnormalities/metabolism/physiopathology
Abstract The assembly of neuronal networks during development requires tightly controlled cell-cell interactions. Multiple cell surface receptors that control axon guidance and synapse maturation have been identified. However, the signaling mechanisms downstream of these receptors have remained unclear. Receptor signals might be transmitted through dedicated signaling lines defined by specific effector proteins. Alternatively, a single cell surface receptor might couple to multiple effectors with overlapping functions. We identified the neuronal RacGAP alpha2-chimaerin as an effector for the receptor tyrosine kinase EphA4. alpha2-Chimaerin interacts with activated EphA4 and is required for ephrin-induced growth cone collapse in cortical neurons. alpha2-Chimaerin mutant mice exhibit a rabbit-like hopping gait with synchronous hindlimb movements that phenocopies mice lacking EphA4 kinase activity. Anatomical and functional analyses of corticospinal and spinal interneuron projections reveal that loss of alpha2-chimaerin results in impairment of EphA4 signaling in vivo. These findings identify alpha2-chimaerin as an indispensable effector for EphA4 in cortical and spinal motor circuits.
Publisher Cell Press
ISSN/ISBN 0896-6273
edoc-URL http://edoc.unibas.ch/dok/A5259843
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.neuron.2007.07.036
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/17785183
ISI-Number WOS:000249857000012
Document type (ISI) Journal Article
 
   

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