Semaphorin4F interacts with the synapse-associated protein SAP90/PSD-95

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Semaphorins are proteins critical for neural development and growth cone guidance.
• SAP90/PSD-95 is a major scaffolding protein in the postsynaptic density of excitatory synapses.

Purpose of the Study:

• To investigate the interaction between Semaphorin4F (Sema4F) and SAP90/PSD-95.
• To elucidate the functional consequences of this interaction at glutamatergic synapses.

Main Methods:

• Yeast two-hybrid system and coprecipitation assays to detect protein interactions.
• Heterologous coexpression in COS cells and deletion analysis to study protein translocation.
• Immunoreactivity analysis in synaptosome and postsynaptic density fractions.
• Colocalization studies in cultured hippocampal neurons using immunofluorescence.

Main Results:

• Semaphorin4F (Sema4F) directly interacts with the PDZ domains of SAP90/PSD-95.
• Sema4F induces the translocation of SAP90/PSD-95 from the cytosol to the membrane, dependent on its C-terminal amino acids.
• Sema4F is localized in synaptosomes and enriched in postsynaptic densities.
• Sema4F colocalizes with SAP90/PSD-95 and synapsin1 in neuronal dendrites, indicating synaptic localization.

Conclusions:

• Semaphorin4F (Sema4F) interacts with SAP90/PSD-95 at glutamatergic synapses.
• This interaction suggests a novel role for semaphorins in synaptic function beyond developmental guidance.
• The findings implicate semaphorins in the molecular architecture and plasticity of excitatory synapses.