TAG-1 can mediate homophilic binding, but neurite outgrowth on TAG-1 requires an L1-like molecule and beta 1 integrins.
Subsets of axons in the embryonic nervous system transiently express the glycoprotein TAG-1, a member of the subfamily of immunoglobulin (Ig)-like proteins that contain both C2 class Ig and fibronectin type III domains. TAG-1 is attached to the cell surface by a glycosylphosphatidylinositol linkage and is secreted by neurons. In vitro studies have shown that substrate-bound TAG-1 promotes neurite outgrowth. We have examined the nature of axonal receptors that mediate the neurite-outgrowth promoting properties of TAG-1. Although TAG-1 can mediate homophilic binding, neurite outgrowth on a substrate of TAG-1 does not depend on the presence of TAG-1 on the axonal surface. Instead, neurite outgrowth on TAG-1 is inhibited by polyclonal antibodies directed against L1 and, independently, by polyclonal and monoclonal antibodies against beta 1-containing integrins. These results provide evidence that TAG-1 can interact with cell surfaces in both a homophilic and heterophilic manner and suggest that neurite extension on TAG-1 requires the function of both integrins and an L1-like molecule.
Felsenfeld
D P
DP
Howard Hughes Medical Institute, Columbia University, New York, New York 10032.
Hynes
M A
MA
Skoler
K M
KM
Furley
A J
AJ
Jessell
T M
TM
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology; D058969:Contactin 2; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000648:ultrastructure; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D013379:Substrate Specificity; D019063:Tenascin
D000906:Antibodies; D015816:Cell Adhesion Molecules, Neuronal; D058969:Contactin 2; D016326:Extracellular Matrix Proteins; D016023:Integrins; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019063:Tenascin