Semaphorin 4B interacts with the post-synaptic density protein PSD-95/SAP90 and is recruited to synapses through a C-terminal PDZ-binding motif

The semaphorins are a large family of proteins that act as guidance signals for axons and dendrites. The class 4 semaphorins are integral membrane proteins that are widely expressed throughout the nervous system. Here, we show that a subclass of these semaphorins is characterized by a PDZ‐binding motif at their carboxy‐terminus. This sequence mediates the interaction with the post‐synaptic density protein PSD‐95/SAP90. Co‐expression of Sema4B with PSD‐95 in COS 7 cells results in the clustering of Sema4B. Sema4B co‐localizes with PSD‐95 at synaptic contacts between cultured hippocampal neurons. This synaptic localization depends on the presence of the PDZ‐binding motif.