Putting the glue in glia: Necls mediate Schwann cell axon adhesion

Abstract

Interactions between Schwann cells and axons are critical for the development and function of myelinated axons. Two recent studies (see Maurel et al. on p. 861 of this issue; Spiegel et al., 2007) report that the nectin-like (Necl) proteins Necl-1 and -4 are internodal adhesion molecules that are critical for myelination. These studies suggest that Necl proteins mediate a specific interaction between Schwann cells and axons that allows proper communication of the signals that trigger myelination.

Figure 1.

Model of interactions between myelinating Schwann cells and axons showing proteins that localize to the node, paranode, juxtaparanode, and internode. Schwann cell, blue; axon, yellow. PN, paranode; JPN, juxtaparanode. Analysis of the Necl proteins provides important new insight into molecular complexes along the internode (Maurel et al., 2007; Spiegel et al., 2007), which had not been as well defined as for the other domains. The polarity protein Par-3 colocalizes with Necl-4 in the adaxonal region of the Schwann cell (Chan et al., 2006), and it is possible that these proteins interact via PDZ and PDZ-binding motifs (red). The Necl proteins can also interact with FERM domain proteins via the FERM-binding domain (blue). Necls are also present at the Schmidt-Lanterman incisures (inset). Necl-2 is not depicted but localizes to the axon–Schwann cell interface and to the incisures. The figure was adapted from Voas et al. (2007).