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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)