The Neurotrophin Receptors TrkA and TrkB are Inhibitory for Neurite Outgrowth

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Abstract
To investigate the possibility that the neurotrophin tyrosine kinase receptors are also recognition molecules by virtue of their immunoglobulin-like domains, the ability of TrkA and TrkB to influence neurite outgrowth was tested in vitro. Cell monolayers of fibroblasts transfected to express either the TrkA or TrkB receptor reduced neurite outgrowth of phaeochromocytoma PC12 cells by 50-60% when compared to mock transfected fibroblasts or fibroblasts transfected with the epidermal growth factor receptor. Neurite outgrowth from cerebellar neurons was inhibited by 30-40% on these substrates. When a recombinantly expressed fragment of TrkA comprising the two immunoglobulin-like domains was coated as a substrate in combination with poly-L-lysine and laminin, neurite outgrowth was inhibited in a dose-dependent manner. This inhibition of neurite outgrowth was not mediated via an interaction with laminin as there is no specific binding of the TrkA fragment to laminin. The adhesion of cell bodies to this substrate was not affected by the immunoglobulin-like domains. These observations suggest that the mammalian neurotrophin receptors not only influence neurite outgrowth by neurotrophin triggered activation of the receptor, but also by cell surface recognition processes conveyed by the immunoglobulin-like domains.