L1-mediated branching is regulated by two ezrin-radixin-moesin (ERM)-binding sites, the RSLE region and a novel juxtamembrane ERM-binding region.
We investigated how the neural cell adhesion molecule L1 mediates neurite outgrowth through L1-L1 homophilic interactions. Wild-type L1 and L1 with mutations in the cytoplasmic domain (CD) were introduced into L1 knock-out neurons, and transfected neurons were grown on an L1 substrate. Neurite length and branching were compared between wild-type L1 and L1CD mutations. Surprisingly, the L1CD is not required for L1-mediated neurite outgrowth but plays a critical role in neurite branching, through both the juxtamembrane region and the RSLE region. We demonstrate that both regions serve as ezrin-moesin-radixin-binding sites. A truncation mutant that deletes 110 of 114 amino acids of the L1CD still supports neurite outgrowth on an L1 substrate, suggesting that a coreceptor binds to L1 in cis and mediates neurite outgrowth and that L1-ankyrin interactions are not essential for neurite initiation or outgrowth. These data are consistent with a model in which L1 can influence L1-mediated neurite outgrowth and branching through both the L1CD and a coreceptor.
Cheng
Ling
L
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Itoh
Kouichi
K
Lemmon
Vance
V
D020816:Amino Acid Motifs; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D002531:Cerebellum / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D039842:Neural Cell Adhesion Molecule L1 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D016501:Neurites / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D017487:Ankyrins; D003598:Cytoskeletal Proteins; D039842:Neural Cell Adhesion Molecule L1