TAG-1 can mediate homophilic binding, but neurite outgrowth on TAG-1 requires an L1-like molecule and B1 integrins

Howard Hughes Medical Institute, Columbia University, New York, New York 10032.
Neuron (Impact Factor: 15.05). 04/1994; 12(3):675-90. DOI: 10.1016/0896-6273(94)90222-4
Source: PubMed


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.

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    • "Subsequent differentiation and connectivity of spinal neurons is governed by an assortment of cell type specific transcription factors, defined as a transcriptional code, that controls the expression of receptors for guidance cues [1], [2]. TAG1 and Nfasc are co-expressed in numerous neuronal cell types in the CNS and PNS; both promote neurite outgrowth [24], [38], [39] and both are required for the architecture and function of nodes of Ranvier [40], [41]. In addition, TAG1 is required in vivo for axon guidance [13], [42], [43], neuronal migration [44], [45], and modulates the responses of sensory axons to diffusible guidance signals by controlling the trafficking of their receptors [43]. "
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    • "A possible mechanism is that knock down of contactin-2 expression inhibits the interaction of contactin-2 with the neural cell adhesion molecule L1 (L1.1 in zebrafish), which was shown to be involved in axonal regeneration of lesioned adult zebrafish [14]. It was also shown that the interaction of contactin-2 with L1 promotes neurite outgrowth in vitro [20], [21]. Since contactin-2 acts by homophilic and heterophilic mechanisms that are conducive to neurite outgrowth, secreted contactin-2 may use these mechanisms for recovery under condition of traumatic injury, particularly in view of the possibility that proteases are activated under conditions of trauma. "
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    • "This complex is required for the clustering of potassium channels at the juxtaparanode in the PNS and in the CNS (Poliak et al. 2003; Savvaki et al. 2008). TAG-1 can also bind heterophically with other cell adhesion molecules such as L1 (Kuhn et al. 1991; Felsenfeld et al. 1994) or NCAM (Milev et al. 1996). Adult TAG-1 null mice show a loss of retinal ganglion cell axons with persistent structural axonal abnormalities linked to myelination defects (Chatzopoulou et al. 2008), as well as shorter internodes in the cerebral and cerebellar white matter (Savvaki et al. 2008). "
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