Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo

The EphA4 receptor tyrosine kinase regulates the formation of the corticospinal tract (CST), a pathway controlling voluntary movements, and of the anterior commissure (AC), connecting the neocortical temporal lobes. To study EphA4 kinase signaling in these processes, we generated mice expressing mutant EphA4 receptors either lacking kinase activity or with severely downregulated kinase activity. We demonstrate that EphA4 is required for CST formation as a receptor for which it requires an active kinase domain. In contrast, the formation of the AC is rescued by kinase-dead EphA4, suggesting that in this structure EphA4 acts as a ligand for which its kinase activity is not required. Unexpectedly, the cytoplasmic sterile-alpha motif (SAM) domain is not required for EphA4 functions. Our findings establish both kinase-dependent and kinase-independent functions of EphA4 in the formation of major axon tracts.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
Animals
Axons/*enzymology
Brain Stem/cytology/embryology/enzymology
Ephrin-A4
Ephrin-B2
Fetal Proteins/deficiency/genetics/*metabolism
In Situ Hybridization
Membrane Proteins/biosynthesis/genetics
Mice
Mice; Knockout
Mice; Mutant Strains
Molecular Sequence Data
Motor Cortex/cytology/embryology/enzymology
Organ Specificity
Prosencephalon/cytology/embryology/enzymology
Protein Structure; Tertiary/genetics
Pyramidal Tracts/cytology/*embryology/*enzymology
RNA; Messenger/biosynthesis
Receptor Protein-Tyrosine Kinases/deficiency/genetics/*metabolism
Receptor; EphA4
Research Support; Non-U.S. Gov't
Signal Transduction/genetics
Temporal Lobe/cytology/embryology

Av författaren/redakt...: Kullander, Klas; Mather, N K; Diella, F; Dottori, M; Boyd, A W; Klein, R

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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