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Image: Neurofascin induced neurite outgrowth. A) Recombinant rat Neurofascin immobilized on a microplate promotes neurite outgrowth in E18 primary rat cortical neurons. B). In absence of the protein, outgrowth is less.
Neurofascin 155 (NF155) is a type I transmembrane glycoprotein that belongs to the L1CAM family of cell adhesion proteins.1,2 The rat NF155 cDNA encodes a 1240 amino acid (aa) precursor that contains a 24 aa signal sequence, a 1086 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 109 aa cytoplasmic domain. The ECD consists of six Ig-like domains and four fibronectin type III repeats, the second of which has an RGD motif. A splice variant of Neurofascin, NF186, lacks the RGD-containing fibronectin type III domain but instead has a mucin-like domain and an additional non-RGD fibronectin type III domain.3 Within shared regions of the ECD, rat NF155 shares 45% and 39% aa sequence identity with rat Nr-CAM and L1CAM, respectively, and 98% aa sequence identity with human and mouse NF155. NF155 is transiently expressed by oligodendrocytes at the onset of axon myelination, whereas NF186 is neuronally expressed in nodes of Ranvier.4-6 Clustering of NF155 in paranodal oligodengroglia lipid raft domains is stabilized by dimerization of its cytoplasmic domains and association with intracellular ankyrin.(6-9) NF155 interacts with axonal contactin and plays a role in node of Ranvier formation and the establishment of saltatory conduction.(5,9-12) The ECD of NF155 is cleaved from oligodengroglia membranes by metalloproteases, a process which is required for NF155 transport from the glial cell body to the axoglial junction.(13) In addition to distinct expression patterns, Neurofascin isoforms have different functional properties. NF155 promotes neuronal adhesion and neurite outgrowth, whereas NF186 inhibits neuronal adhesion.(4,7,13).