Class A Plexins Are Organized as Preformed Inactive Dimers on the Cell Surface

Area of Science:

• Cell biology
• Molecular biology
• Neuroscience

Background:

• Plexins are single-pass transmembrane receptors crucial for axon guidance, binding semaphorin ligands.
• Receptor activation often involves ligand-induced dimerization or conformational changes, challenging to study in live cells.

Purpose of the Study:

• To investigate the dimerization state of PlexinA4 in live cells.
• To determine how semaphorin binding affects PlexinA4 dimerization and activation.

Main Methods:

• Pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS), a live-cell microscopy technique.
• Analysis of full-length PlexinA4, control proteins, and plexin mutants.

Main Results:

• Inactive PlexinA4 exists as dimers in the plasma membrane.
• Dimerization requires the Sema domain but not the cytoplasmic domain.
• Semaphorin 6A binding does not increase plexin oligomerization.

Conclusions:

• Semaphorin activation involves disrupting inhibitory PlexinA4 dimers.
• This disruption leads to the formation of a specific active plexin dimer.
• The Sema domain is critical for maintaining the inactive dimeric state.