Syndecan-3 and syndecan-4 are enriched in Schwann cell perinodal processes

Background: Nodes of Ranvier correspond to specialized axonal domains where voltage-gated sodium channels are highly concentrated. In the peripheral nervous system, they are covered by Schwann cells microvilli, where three homologous cytoskeletal-associated proteins, ezrin, radixin and moesin (ERM proteins) have been found, to be enriched. These glial processes are thought to play a crucial role in organizing axonal nodal domains during development. However, little is known about the molecules present in Schwann cell processes that could mediate axoglial interactions. The aim of this study is to identify by immunocytochemistry transmembrane proteins enriched in Schwann cells processes that could interact, directly or indirectly, with axonal proteins. Results: We show that syndecan-3 (S3) and syndecan-4 (S4), two proteoglycans expressed in Schwann cells, are enriched in perinodal processes in rat sciatic nerves. S3 labeling was localized in close vicinity of sodium channels as early as post-natal day 2, and highly concentrated at nodes of Ranvier in the adult. S4 immunoreactivity accumulated at nodes later, and was also prominent in internodal regions of myelinated fibers. Both S3 and S4 were co-localized with ezrin in perinodal processes. Conclusions: Our data identify S3 and S4 as transmembrane proteins specifically enriched in Schwann cell perinodal processes, and suggest that S3 may be involved in early axoglial interactions during development.