BMPs Regulate Ionotropic Glutamate Receptors
Dennis Higgins Principal Investigator
Jerome Roth Principal Investigator
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Bone morphogenetic proteins (BMPs) regulate many aspects of neural development and they are also neuroprotective in mature animals. It is, therefore, important to understand the mechanism of action of these neurotrophic factors. Previous studies of BMP signaling pathways have focused on the transcriptional activities of these proteins and have emphasized their ability to alter neural cell fate by inducing or repressing gene expression. Preliminary studies from this laboratory, however, indicate that BMPs can also induce rapid (<1 second) changes in the conductance state of ionotropic glutamate receptors and that this occurs in both mature (adult human retinal) and developing (rat hippocampal) neural cell populations. Thus, there may be a second, parallel pathway for BMP signaling that acts independently of nuclear events and that alters neural function by acutely regulating existing ion channels in cultured neurons. The experiments in this project will characterize this pathway by comparing the effects of BMPs on the three types of ionotropic glutamate receptors and by determining whether BMPs also affect voltage-sensitive ion channels. In addition, the project will characterize the types of receptors mediating the effects of BMPs on glutamate receptors and will determine whether BMPs modulate glutamatergic synaptic transmission in tissue culture. It is anticipated that these experiments will substantially expand our knowledge of BMP signaling mechanisms and that they will also provide an initial assessment of the ability of BMPs to function as synaptic modulators.