PT - JOURNAL ARTICLE AU - Masaaki Sato AU - Kazunori Suzuki AU - Shigetada Nakanishi TI - NMDA Receptor Stimulation and Brain-Derived Neurotrophic Factor Upregulate Homer 1a mRNA via the Mitogen-Activated Protein Kinase Cascade in Cultured Cerebellar Granule Cells AID - 10.1523/JNEUROSCI.21-11-03797.2001 DP - 2001 Jun 01 TA - The Journal of Neuroscience PG - 3797--3805 VI - 21 IP - 11 4099 - http://www.jneurosci.org/content/21/11/3797.short 4100 - http://www.jneurosci.org/content/21/11/3797.full SO - J. Neurosci.2001 Jun 01; 21 AB - In three alternative splice variants of Homer 1 transcripts, Homer 1a mRNA has been shown to be upregulated selectively and rapidly by neural stimulation and represents a member of the immediate early gene (IEG) family. We investigated the mechanism underlying Homer 1a mRNA induction in cerebellar granule cell culture. All Homer 1 variants were expressed in cultured granule cells as analyzed by RNA blotting and immunochemical characterization. Glutamate stimulation of granule cells selectively upregulated Homer 1a mRNA via NMDA receptor-mediated influx of extracellular calcium. The induction of Homer 1a mRNA was much slower (peaked at 4 hr) and sustained longer than that of the typical IEG c-fos mRNA. Actinomycin D and cycloheximide experiments have revealed that, despite the presence of the mRNA-destabilizing AU-rich motif, transcriptional activation is a main determinant for selective Homer 1a mRNA induction. Inhibitor analysis as well as immunochemical characterization has indicated that the MEK (MAPK/ERK kinase)–ERK (extracellular signal-regulated kinase) cascade plays an indispensable role in glutamate-stimulated induction of Homer 1a mRNA. Consistent with this observation, brain-derived neurotrophic factor, which is known to activate the ERK cascade, similarly upregulated Homer 1a mRNA. These results demonstrate that MAPK (mitogen-activated protein kinase) is a key mediator that links distinct extracellular stimuli to the transcriptional activation of Homer 1a mRNA.