Functional binding interaction identified between the axonal CAM L1 and members of the ERM family.
A yeast two-hybrid library was screened using the cytoplasmic domain of the axonal cell adhesion molecule L1 to identify binding partners that may be involved in the regulation of L1 function. The intracellular domain of L1 bound to ezrin, a member of the ezrin, radixin, and moesin (ERM) family of ... membrane-cytoskeleton linking proteins, at a site overlapping that for AP2, a clathrin adaptor. Binding of bacterial fusion proteins confirmed this interaction. To determine whether ERM proteins interact with L1 in vivo, extracellular antibodies to L1 were used to force cluster the protein on cultured hippocampal neurons and PC12 cells, which were then immunolabeled for ERM proteins. Confocal analysis revealed a precise pattern of codistribution between ERMs and L1 clusters in axons and PC12 neurites, whereas ERMs in dendrites and spectrin labeling remained evenly distributed. Transfection of hippocampal neurons grown on an L1 substrate with a dominant negative ERM construct resulted in extensive and abnormal elaboration of membrane protrusions and an increase in axon branching, highlighting the importance of the ERM-actin interaction in axon development. Together, our data indicate that L1 binds directly to members of the ERM family and suggest this association may coordinate aspects of axonal morphogenesis.
Mesh Terms:
Actins, Adaptor Protein Complex 2, Adaptor Proteins, Vesicular Transport, Amino Acid Substitution, Animals, Ankyrins, Antigens, Surface, Carrier Proteins, Cell Adhesion Molecules, Cell Differentiation, Cytoplasm, Cytoskeletal Proteins, DNA-Binding Proteins, Hippocampus, Humans, Leukocyte L1 Antigen Complex, Membrane Glycoproteins, Membrane Proteins, Morphogenesis, Neural Cell Adhesion Molecules, PC12 Cells, Phosphoproteins, Rats, Rats, Sprague-Dawley, Transcription Factors
Actins, Adaptor Protein Complex 2, Adaptor Proteins, Vesicular Transport, Amino Acid Substitution, Animals, Ankyrins, Antigens, Surface, Carrier Proteins, Cell Adhesion Molecules, Cell Differentiation, Cytoplasm, Cytoskeletal Proteins, DNA-Binding Proteins, Hippocampus, Humans, Leukocyte L1 Antigen Complex, Membrane Glycoproteins, Membrane Proteins, Morphogenesis, Neural Cell Adhesion Molecules, PC12 Cells, Phosphoproteins, Rats, Rats, Sprague-Dawley, Transcription Factors
J. Cell Biol.
Date: Jun. 24, 2002
PubMed ID: 12070130
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