Recombinant Human CHL-1/L1CAM-2 Protein, CF

Close homolog of L1 (CHL-1), also known as cell adhesion L1-like (CALL) and L1 cell adhesion molecule 2 (L1-CAM2), belongs to the L1 subfamily of the Ig superfamily cell adhesion molecules, which also include L1, neurofascin and NgCAM-related cell adhesion molecule (NrCAM) (1 - 3). These molecules are type I transmembrane proteins that have 6 Ig-like domains and 4 - 5 fibronectin type III-like (FNIII) domains in their extracellular regions. They also shared a highly conserved cytoplasmic region of approximately 110 amino acid residues (aa) containing an ankyrin-binding site. CHL-1 is expressed as a highly glycosylated 185 kDa transmembrane protein by subpopulations of neurons and glia of the central and peripheral nervous system (4, 5). Ectodomain shedding via the metalloprotease-disintegrin ADAM8 releases 165 kDa and 125 kDa soluble CHL-1 fragments, which can diffuse away to function at distant sites (6). CHL-1 is not capable of homotypic interactions, but an extracellular binding partner of CHL-1 has not been identified (4). Human CHL1 has been mapped to chromosome 3p26 and is a candidate gene for 3p^- syndrome characterized by mental impairment (7). A missense CHL1 polymorphism associated with an increased risk of schizophrenia has been reported (8). The functional importance of CHL-1 in the nervous system is also evident in CHL-1 deficient mice, which display behavioral abnormalities and show misguided axons within the hippocampus and olfactory tract (9). Enhanced ectodomain-shedding of CHL-1 is also observed in Wobbler mice, the neurodegenerative mutant mice (6). In vitro, soluble or substrate-coated CHL-1 promotes neurite outgrowth and neuronal survival of both cerebellar and hippocampal neurons. Cell surface CHL-1 interacts with integrins in cis to potentiate integrin-dependent cell migration toward extracellular matrix proteins (10). For this enhanced cell motility, CHL-1 linkage to the actin cytoskeleton via interaction between ankyrin and the CHL-1 cytoplasmic region is required.