Cis interaction between Semaphorin6A and Plexin-A4 modulates the repulsive response to Sema6A

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Axon guidance is crucial for neural circuit formation.
• Differential receptor expression on axons determines responsiveness to guidance cues.
• Transmembrane Semaphorin Sema6A is a key guidance molecule.

Purpose of the Study:

• To investigate the role of Semaphorin Sema6A (Sema6A) co-expression with its receptor Plexin-A4 (Plexin-A4) in determining neuronal responsiveness.
• To elucidate the mechanism by which Sema6A influences axon guidance in sympathetic and sensory neurons.

Main Methods:

• Comparative analysis of Sema6A and Plexin-A4 expression in sympathetic and sensory neurons.
• Functional assays using heterologous systems to assess neuronal responsiveness to Sema6A.
• Investigation of cis- versus trans-interactions between Sema6A and Plexin-A4.

Main Results:

• Both sympathetic and sensory neurons express Plexin-A4, but only sensory neurons express Sema6A.
• Sensory neurons expressing Sema6A are unresponsive to Sema6A, while sympathetic neurons are responsive.
• Sensory neurons lacking Sema6A gain sensitivity to Sema6A in a Plexin-A4-dependent manner.
• Sema6A and Plexin-A4 co-expression in cis inhibits ligand binding, suggesting an inhibitory cis-interaction.

Conclusions:

• Co-expression of a transmembrane guidance cue and its receptor acts as a modulator of neuronal responsiveness.
• A cis-interaction between Sema6A and Plexin-A4 inhibits axon guidance.
• Differential expression of guidance cues and their receptors dictates axon navigation specificity.