Increased calcium triggers several different responses in nerve cells including long term changes that are thought to be mediated through alterations in gene expression. These experiments seek to investigate the mechanism whereby calcium increases expression of the immediate early gene c-fos. Previous research by the applicant has led to the model that a calcium-calmodulin complex activates a calcium-regulated kinase that activates CREB at serine- 133. This may then lead to the binding of CBP to the phosphorylated CREB, which then promotes activation of c-fos. The applicant intends to continue investigating this activation by 1) identifying proposed factors that bind to CREB to form heterodimers; 2) characterizing a second event needed for CREB- mediated transcriptional activation; and 3) identifying the kinase responsible for CREB phosphorylation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS028829-10
Application #
2714490
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Leblanc, Gabrielle G
Project Start
1990-08-01
Project End
1999-08-31
Budget Start
1998-06-01
Budget End
1999-08-31
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Hrvatin, Sinisa; Hochbaum, Daniel R; Nagy, M Aurel et al. (2018) Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat Neurosci 21:120-129
Mardinly, A R; Spiegel, I; Patrizi, A et al. (2016) Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons. Nature 531:371-5
Andzelm, Milena M; Cherry, Timothy J; Harmin, David A et al. (2015) MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers. Neuron 86:247-63
Bloodgood, Brenda L; Sharma, Nikhil; Browne, Heidi Adlman et al. (2013) The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature 503:121-5
Chahrour, Maria H; Yu, Timothy W; Lim, Elaine T et al. (2012) Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. PLoS Genet 8:e1002635
Hemberg, Martin; Gray, Jesse M; Cloonan, Nicole et al. (2012) Integrated genome analysis suggests that most conserved non-coding sequences are regulatory factor binding sites. Nucleic Acids Res 40:7858-69
Ross, Sarah E; McCord, Alejandra E; Jung, Cynthia et al. (2012) Bhlhb5 and Prdm8 form a repressor complex involved in neuronal circuit assembly. Neuron 73:292-303
Ross, Sarah E; Mardinly, Alan R; McCord, Alejandra E et al. (2010) Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron 65:886-98
Kim, Tae-Kyung; Hemberg, Martin; Gray, Jesse M et al. (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465:182-7
Greer, Paul L; Hanayama, Rikinari; Bloodgood, Brenda L et al. (2010) The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell 140:704-16

Showing the most recent 10 out of 41 publications