Sema4C, a transmembrane semaphorin, interacts with a post-synaptic densityprotein, PSD-95

Semaphorins are known to act as chemorepulsive molecules that guide axons d uring neural development. Sema4C, a group 4 semaphorin, is a transmembrane semaphorin of unknown function. The cytoplasmic domain of Sema4C contains a proline-rich region that may interact with some signaling proteins. In thi s study, we demonstrate that Sema4C is enriched in the adult mouse brain an d associated with PSD-95 isoforms containing PDZ (PSD-95/DLG/ZO-1) domains, such as PSD-95/SAP90, PSD-93/chapsin110, and SAP97/DLG-1, which are concen trated in the post-synaptic density of the brain. In the neocortex, S4C is enriched in the synaptic vesicle fraction and Triton X-100 insoluble post-s ynaptic density fraction. Immunostaining for Sema4C overlaps that for PSD-9 5 in superficial layers I-IV of the neocortex. In neocortical culture, S4C is colocalized with PSD-95 in neurons, with a dot-like pattern along the ne urites. Sema4C thus may function in the cortical neurons as a hi-directiona l transmembrane ligand through interacting with PSD-95.