Disease-associated mutations in L1 CAM interfere with ligand interactions and cell-surface expression

Item Type:	Article
Title:	Disease-associated mutations in L1 CAM interfere with ligand interactions and cell-surface expression
Creators Name:	De Angelis, E. and Watkins, A. and Schaefer, M. and Bruemmendorf, T. and Kenwrick, S.
Abstract:	Mutations in the L1CAM gene cause a highly variable neurological disease described as X-linked hydrocephalus, MASA syndrome or spastic paraplegia type I. Over one-third of the mutations identified in affected boys are missense, unique to individual families and distributed primarily across the large extracellular domain of the L1 protein. We have examined the effects of 25 missense mutations on binding to homophilic (L1) and heterophilic (TAX-1) ligands as well as on intracellular trafficking. All but three of these result in reduced ligand binding or impaired movement to the surface of COS and CHO cells. Therefore, we demonstrate for the first time that most missense mutations found in affected families have functional consequences. Furthermore, mutations that are predicted to affect the structure of individual extracellular domains are more likely to affect intracellular processing and/or ligand binding than those mutations affecting surface properties of the molecule.
Keywords:	Animals, Cell Adhesion, Cell Membrane, COS Cells, DNA Primers, Gene Deletion, Hydrocephalus, Leukocyte L1 Antigen Complex, Ligands, Membrane Glycoproteins, Missense Mutation, Mutagenesis, Neural Cell Adhesion Molecules, Neuronal Cell Adhesion Molecules, Polymerase Chain Reaction, Protein Binding, Protein Transport, Recombinant Proteins, Surface Antigens, X Chromosome
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	11
Number:	1
Page Range:	1-12
Date:	1 January 2002
Official Publication:	http://hmg.oxfordjournals.org/cgi/content/abstract/11/1/1
PubMed:	View item in PubMed

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