Phosphorylation of the transcription factor Sp4 is reduced by NMDA receptor signaling
Article first published online: 12 FEB 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 129, Issue 4, pages 743–752, May 2014
How to Cite
J. Neurochem. (2014) 129, 743–752.
- Issue published online: 23 APR 2014
- Article first published online: 12 FEB 2014
- Accepted manuscript online: 29 JAN 2014 12:14PM EST
- Manuscript Accepted: 9 JAN 2014
- Manuscript Revised: 6 JAN 2014
- Manuscript Received: 4 NOV 2013
- NIH. Grant Number: RO1 HD043364
- NIH NINDS. Grant Number: T32 NS061764
- cerebellar granule neurons;
- NMDA receptor;
- transcription factor Sp4
The regulation of transcription factor function in response to neuronal activity is important for development and function of the nervous system. The transcription factor Sp4 regulates the developmental patterning of dendrites, contributes to complex processes including learning and memory, and has been linked to psychiatric disorders such as schizophrenia and bipolar disorder. Despite its many roles in the nervous system, the molecular mechanisms regulating Sp4 activity are poorly understood. Here, we report a site of phosphorylation on Sp4 at serine 770 that is decreased in response to membrane depolarization. Inhibition of the voltage-dependent NMDA receptor increased Sp4 phosphorylation. Conversely, stimulation with NMDA reduced the levels of Sp4 phosphorylation, and this was dependent on the protein phosphatase 1/2A. A phosphomimetic substitution at S770 impaired the Sp4-dependent maturation of cerebellar granule neuron primary dendrites, whereas a non-phosphorylatable Sp4 mutant behaved like wild type. These data reveal that transcription factor Sp4 is regulated by NMDA receptor-dependent activation of a protein phosphatase 1/2A signaling pathway. Our findings also suggest that the regulated control of Sp4 activity is an important mechanism governing the developmental patterning of dendrites.
We show that the neuronal transcription factor Sp4, which regulates the developmental patterning of dendrites, is dephosphorylated at S770 in response to NMDA receptor signaling in cerebellar granule neurons and cortical neurons. Dephosphorylation required the activity of the PP1/PP2A phosphatase. A point mutation at S770 to a phosphomimetic aspartic acid residue impaired Sp4-dependent pruning of cerebellar granule neuron primary dendrites.