DIgLONs inhibit initiation of neurite outgrowth from forebrain neurons via an IgLON-containing receptor complex

• Published in: Brain research Vol. 1374; pp. 27 - 35
• Main Authors: Akeel, Mohammed, McNamee, Christine J, Youssef, Sahar, Moss, Diana
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 16-02-2011; Elsevier
• Subjects: Animals; Avian Proteins - physiology; Axon guidance; Biological and medical sciences; brain; cell adhesion; Cell adhesion molecule; Cell Line, Tumor; Cell physiology; Chick Embryo; chicks; CHO Cells; Cricetinae; Cricetulus; Forebrain neuron; Fundamental and applied biological sciences. Psychology; G-protein coupled receptors; GPI-anchored glycoprotein; Growth Inhibitors - physiology; Heterodimeric complex; Immunoglobulins - physiology; Membrane Glycoproteins - physiology; Membrane Proteins - physiology; Mice; Miscellaneous; Molecular and cellular biology; Neural Cell Adhesion Molecules - physiology; Neural Inhibition - physiology; Neurites - physiology; Neurology; neurons; Neurons - physiology; pertussis toxin; Prosencephalon - physiology; tumor suppressor genes; Forebrain neuron; fluorescent activated cell sorting; PIPLC; Cell adhesion molecule; Pertussis Toxin; embryonic day 6, 7, 8; FACS; Dimeric IgLON; E6, E7, E8; PTX; DIgLON; Heterodimeric complex; GPI-anchored glycoprotein; Axon guidance; Phosphatidyl inositol phospholipase C; Neurite; Growth; Central nervous system; Glycoprotein; Axon; Prosencephalon; Guidance; Neuron; Biological receptor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2010.12.028

Abstract IgLONs are a family of four GPI-anchored cell adhesion molecules that regulate neurite outgrowth, synaptogenesis and may act as tumour suppressor genes. IgLONs are thought to function as monomers or homodimers and we have proposed that IgLONs also act as heterodimeric complexes termed Dimeric IgLONs or DIgLONs. Here we show that the initiation of neurite outgrowth is inhibited from a subset of chick embryonic day (E) 7 or 8 forebrain neurons when they are cultured on CHO cell lines expressing DIgLON:CEPU-1-OBCAM and DIgLON:CEPU-1-LAMP but not on CHO cells that express single IgLONs CEPU-1 or OBCAM. Surprisingly at the younger age of E6 forebrain neurons do not respond to DIgLONs. Since there is little difference in expression of IgLONs on the surface of chick forebrain neurons at these two ages we suggest IgLONs alone are not the receptor on the responding forebrain neurons. A DIgLON heterodimeric recombinant protein DIgLON:CEPU-1-OBCAM-Fc also blocked neurite outgrowth from E8 chick forebrain neurons. However, when IgLONs were removed from the surface of these E8 neurons they no longer responded to DIgLON:CEPU-1-OBCAM-Fc substrate, indicating that IgLONs form at least a component of the neuronal cell receptor complex involved in this inhibition of neurite outgrowth. Inhibitors pertussis toxin and Y27632 reversed the inhibition of neurite outgrowth on a DIgLON:CEPU-1-OBCAM and DIgLON:CEPU-1-LAMP substrate. This suggests the involvement of a G-protein coupled receptor and activation of Rho A. In summary we provide evidence that DIgLON:CEPU-1-OBCAM and DIgLON:CEPU-1-LAMP complexes regulate initiation of neurite outgrowth on forebrain neurons via an IgLON-containing receptor complex.