NEUROTROPHIC FACTOR RECEPTORS AND THEIR SIGNAL-TRANSDUCTION CAPABILITIES IN RAT ASTROCYTES

Until recently, astrocytes were not considered as sites for neurotroph ic factor action. We show here that, both in vivo and in vitro, astroc ytes express receptors for two separate families of neurotrophic facto rs. In the intact adult rat CNS, astrocytes express the extracellular domain of the neurotrophin receptor TrkB and, in a more restricted pop ulation, the low-affinity nerve growth factor receptor p75(LNGFR). In the lesioned CNS, expression of the alpha component of the receptor fo r ciliary neurotrophic factor (CNTFR alpha) switches from a purely neu ronal localization to cells in the glial scar at the edge of the wound . Using cultured hippocampal astrocytes as a model to address the func tional status of these receptors, we have found only the truncated for ms of TrkB and TrkC, which are incapable of signal transduction as mea sured by protein tyrosine phosphorylation or immediate early gene indu ction. In contrast, a fully functional CNTF receptor complex capable o f signal transduction is present on cultured astrocytes. Thus, the neu rotrophin receptors may act primarily to sequester or present the neur otrophins, whereas in the case of CNTF a functional response can be in itiated within the astrocyte.