AL-1-induced growth cone collapse of rat cortical neurons is correlated with REK7 expression and rearrangement of the actin cytoskeleton.

Abstract

Previous experiments identified AL-1 as a glycosylphosphatidylinositol (GPI)-linked ligand for the Eph-related receptor, REK7, and showed that a REK7-IgG fusion protein blocks axon bundling in co-cultures of cortical neurons on astrocytes, suggesting a role for REK7 and AL-1 in axon fasciculation. Subsequent identification of RAGS, the chick homologue of AL-1, as a repellent axon guidance molecule in the developing chick visual system led to speculation that AL-1, expressed on astrocytes, provides a repellent stimulus for cortical axons, inducing them to bundle as an avoidance mechanism. Using a growth cone collapse assay to test this hypothesis, we show that a soluble AL-1-IgG fusion protein is a potent collapsing factor for embryonic rat cortical neurons. The response is strongly correlated with REK7 expression, implicating REK7 as a receptor mediating AL-1-induced collapse. Morphological collapse is preceded by an AL-1-IgG-induced reorganization of the actin cytoskeleton that resembles the effects of cytochalasin D. This suggests a pathway whereby REK7 activation by AL-1 leads to perturbation of the actin cytoskeleton, possibly by an effect on actin polymerization, followed by growth cone collapse. We further show that AL-1-IgG causes collapse of rat hippocampal neurons and rat retinal ganglion cells. These data suggest a role for REK7 and AL-1 in the patterning of axonal connections in the developing cortex, hippocampus and visual system.

• Authors: L Meima, I J Kljavin, P Moran, A Shih, J W Winslow, I W Caras
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 9 Issue 1 Pg. 177-88 (Jan 1997) ISSN: 0953-816X [Print] France
• PMID: 9042581 (Publication Type: Journal Article)

Chemical References

• Actins
• CD4 Antigens
• Ephrin-A2
• Glycosylphosphatidylinositols
• Ligands
• Rhodamines
• Transcription Factors
• Receptor Protein-Tyrosine Kinases

Topics

• Actins (biosynthesis)
• Animals
• CD4 Antigens (metabolism)
• Cerebral Cortex (drug effects, growth & development, metabolism)
• Cytoskeleton (drug effects, metabolism)
• Ephrin-A2
• Fluorescent Antibody Technique, Indirect
• Glycosylphosphatidylinositols (pharmacology)
• Histocytochemistry
• Ligands
• Neurons (drug effects, metabolism, physiology)
• Rats
• Receptor Protein-Tyrosine Kinases (biosynthesis, genetics)
• Retina (cytology)
• Rhodamines
• Transcription Factors (pharmacology)
• Visual Cortex (cytology, growth & development)