Alternative use of a mini exon of the L1 gene affects L1 binding to neural ligands.
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.
De Angelis
E
E
Wellcome Trust Centre for Molecular Mechanisms in Disease and Cambridge University, Cambridge CB2 2XY, United Kingdom. ed214@mole.bio.cam.ac.uk
Brummendorf
T
T
Cheng
L
L
Lemmon
V
V
Kenwrick
S
S
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002531:Cerebellum / Q000502:physiology; D017931:DNA Primers; D005091:Exons; D006801:Humans; D007668:Kidney / Q000502:physiology; D039841:Leukocyte L1 Antigen Complex; D008024:Ligands; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology; D017384:Sequence Deletion
D000954:Antigens, Surface; D017931:DNA Primers; D039841:Leukocyte L1 Antigen Complex; D008024:Ligands; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D011994:Recombinant Proteins