Analysis of interactions of the adhesion molecule TAG-1 and its domains with other immunoglobulin superfamily members.
Cell adhesion molecules of the immunoglobulin superfamily promote cell aggregation and neurite outgrowth via homophilic and heterophilic interactions. The transient axonal glycoprotein TAG-1 induces cell aggregation through homophilic interaction of its fibronectin repeats. We investigated the domains responsible for the neurite outgrowth promoting activity of TAG-1 as well as its interactions with other cell adhesion molecules. Binding experiments with Fc-chimeric proteins revealed that TAG-1 interacts with L1, NrCAM, and F3/contactin. The membrane-associated as opposed to the soluble form of TAG-1 behaves differently in these assays. We demonstrate that both the immunoglobulin as well as the fibronectin domains promote neurite outgrowth when used as substrates. Furthermore we investigated the putative role of L1 and NrCAM as the neuronal TAG-1 receptors mediating neurite extension. DRG neurons from L1-deficient mice were found to extend neurites on TAG-1 substrates and blocking NrCAM function did not diminish the TAG-1-dependent neurite outgrowth. These results indicate that neither L1 nor NrCAM are required for TAG-1-elicited neurite outgrowth.
Pavlou
Ourania
O
Department of Basic Science, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, P.O. Box 1527, Heraklion, Greece.
Theodorakis
Kostas
K
Falk
Julien
J
Kutsche
Michael
M
Schachner
Melitta
M
Faivre-Sarrailh
Catherine
C
Karagogeos
Domna
D
D000818:Animals; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002645:Chickens; D058969:Contactin 2; D006224:Cricetinae; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D005810:Multigene Family; D016501:Neurites / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats
C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D007136:Immunoglobulins