Cell Adhesion Molecules NgCAM and Axonin-1 Form Heterodimers in the Neuronal Membrane and Cooperate in Neurite Outgrowth Promotion

• Published in: The Journal of cell biology 1996-12, Vol.135 (6), p.1593-1607
• Main Authors: Buchstaller, Andrea, Kunz, Stefan, Berger, Philipp, Kunz, Beat, Ziegler, Urs, Rader, Christoph, Sonderegger, Peter
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies; Antibodies - immunology; Base Sequence; Cell adhesion; Cell Adhesion Molecules, Neuron-Glia - chemistry; Cell Adhesion Molecules, Neuron-Glia - physiology; Cell Adhesion Molecules, Neuronal - chemistry; Cell Adhesion Molecules, Neuronal - immunology; Cell Adhesion Molecules, Neuronal - physiology; Cell aggregates; Cell Aggregation; Cell Line; Cell Membrane - chemistry; Cell Membrane - physiology; Cells; Cellular biology; Chick Embryo; Contactin 2; COS Cells; Dimerization; DNA; Growth cones; Membranes; Molecular Sequence Data; Molecules; Neurites; Neurites - physiology; Neurons; Polymerase Chain Reaction; Sensory perception; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.135.6.1593

The axonal surface glycoproteins neuron-glia cell adhesion molecule (NgCAM) and axonin-1 promote cell-cell adhesion, neurite outgrowth and fasciculation, and are involved in growth cone guidance. A direct binding between NgCAM and axonin-1 has been demonstrated using isolated molecules conjugated to the surface of fluorescent microspheres. By expressing NgCAM and axonin-1 in myeloma cells and performing cell aggregation assays, we found that NgCAM and axonin-1 cannot bind when present on the surface of different cells. In contrast, the cocapping of axonin-1 upon antibody-induced capping of NgCAM on the surface of CV-1 cells coexpressing NgCAM and axonin-1 and the selective chemical cross-linking of the two molecules in low density cultures of dorsal root ganglia neurons indicated a specific and direct binding of axonin-1 and NgCAM in the plane of the same membrane. Suppression of the axonin-1 translation by antisense oligonucleotides prevented neurite outgrowth in dissociated dorsal root ganglia neurons cultured on an NgCAM substratum, indicating that neurite outgrowth on NgCAM substratum requires axonin-1. Based on these and previous results, which implicated NgCAM as the neuronal receptor involved in neurite outgrowth on NgCAM substratum, we concluded that neurite outgrowth on an NgCAM substratum depends on two essential interactions of growth cone NgCAM: a trans-interaction with substratum NgCAM and a cis-interaction with axonin-1 residing in the same growth cone membrane.