Abstract
Neural cell adhesion molecule L1 is a cell surface glycoprotein required for the correct development of the nervous system. L1 exists as two isoforms encoded by mRNA species that either collectively incorporate or exclude exons 2 and 27. Neurons utilize only the full-length isoform, whereas Schwann cells, kidney cells, and blood lymphocytes only express the short form of L1. Still other cells, oligodendrocytes, regulate L1 isoform expression in a maturation-dependent manner. The RSLE motif encoded by exon 27 is known to have a role in clathrin-mediated endocytosis of L1, but the function of the exon 2-encoded motif (YEGHHV) is unknown. Here we show that this motif is required for the optimal binding of L1 to several neural ligands and is likely to be important for nervous system development. Thus, alternative use of exon 2 is a mechanism for regulating ligand interactions with L1.
Highlights
Neural cell adhesion molecule L1 is one member of a subfamily of immunoglobulin (Ig) superfamily proteins that acts as a cellular and axonal guidance cue and receptor during nervous system development
Homophilic interaction is likely to be an important mediator of neurite outgrowth in nervous system development, because explanted neurons will extend neurites on an L1 substrate only if L1 is present as a receptor
To investigate whether the alternative splicing of exon 2 has an influence on cell surface interactions, binding assays were conducted for three ligands, L1 and glycophosphatidylinositollinked Ig superfamily members TAX-1 and F3, for the following
Summary
Neural cell adhesion molecule L1 is one member of a subfamily of immunoglobulin (Ig) superfamily proteins that acts as a cellular and axonal guidance cue and receptor during nervous system development. We have examined the influence of the exon 2 motif on L1 trafficking in neuronal cells and on the ability of L1 to bind to itself and two other Ig superfamily ligands found primarily in the nervous system, TAX-1 (rodent TAG-1/chick axonin-1) and contactin (rodent F3/chick F11). Reduced binding has been found for patient mutations that cause Xlinked hydrocephalus [12], indicating that exon 2-encoded residues are required for the neuronal function of L1.
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