A central role for Necl4 (SynCAM4) in Schwann cell–axon interaction and myelination

Abstract

Myelination in the peripheral nervous system requires close contact between Schwann cells and the axon, but the underlying molecular basis remains largely unknown. Here we show that cell adhesion molecules (CAMs) of the Nectin-like (Necl, also known as SynCAM or Cadm) family mediate Schwann cell-axon interaction during myelination. Necl4 is the main Necl expressed by myelinating Schwann cells and is located along the internodes in direct apposition to Necl1, which is localized on axons. Necl4 serves as the glial binding partner for axonal Necl1, and the interaction between these two CAMs mediates Schwann cell adhesion. Furthermore, the disruption of the interaction between Necl1 and Necl4 by their soluble extracellular domains, as well as the expression of a dominant negative Necl4 in Schwann cells, inhibits myelination. These results suggest a critical role for Necl proteins in mediating axon-glia contact during myelination in peripheral nerves.

Six cadm/synCAM genes are expressed in the nervous system of developing zebrafish

“…5K,L). This finding may reflect the expression of cadm3 and 4 in both neurons and glial cells, as has been demonstrated in the mouse (Kakunaga et al, 2005;GruberOlipitz et al, 2006;Maurel et al, 2007;Spiegel et al, 2007).…”

“…The Cadms (cell adhesion molecules) are a family of type I transmembrane proteins that have been described in several pathological and physiological processes such as the progression of lung and other cancers (reviewed in Murakami, 2005), mast cell adhesion (Ito et al, 2003(Ito et al, , 2007bFuruno et al, 2005;Ito and Oonuma, 2006), spermatogenesis (Wakayama et al, 2001;Wakayama et al, 2003;Fujita et al, 2006;van der Weyden et al, 2006;Yamada et al, 2006), epithelium development and homeostasis (Ito et al, 2007b), and central nervous system development (Biederer et al, 2002;Sara et al, 2005;Spiegel et al, 2007).…”

“…In contrast to Cadm1, Cadm3 and Cadm4 expression seems to be mostly restricted to neurons and glial cells (astrocytes, oligodendrocytes, and Schwann cells; Maurel et al, 2007;Spiegel et al, 2007). Recently, it has been proposed that a heterophilic interaction between Cadm3 and Cadm4 mediates Schwann cell adhesion to peripheral axons.…”

“…Recently, it has been proposed that a heterophilic interaction between Cadm3 and Cadm4 mediates Schwann cell adhesion to peripheral axons. Perturbation with dominant-negative forms of either Cadm3 or Cadm4 or knockdown of their expression blocks the myelination process (Maurel et al, 2007;Spiegel et al, 2007). Expression patterns and function of Cadm2 have not been reported to date.…”

Nectines et nectines-like

“…Necl-1 a une expression limitée au tissu neural où elle joue un rôle dans la synaptogenèse et la myélinisation du système nerveux [33]. L'expression de necl-1 est perdue dans des gliomes.…”