scholarly journals PKA-activated ApAF–ApC/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation

2006 ◽  
Vol 174 (6) ◽  
pp. 827-838 ◽  
Author(s):  
Jin-A Lee ◽  
Sue-Hyun Lee ◽  
Changhoon Lee ◽  
Deok-Jin Chang ◽  
Yong Lee ◽  
...  

Long-term memory requires transcriptional regulation by a combination of positive and negative transcription factors. Aplysia activating factor (ApAF) is known to be a positive transcription factor that forms heterodimers with ApC/EBP and ApCREB2. How these heterodimers are regulated and how they participate in the consolidation of long-term facilitation (LTF) has not, however, been characterized. We found that the functional activation of ApAF required phosphorylation of ApAF by PKA on Ser-266. In addition, ApAF lowered the threshold of LTF by forming a heterodimer with ApCREB2. Moreover, once activated by PKA, the ApAF–ApC/EBP heterodimer transactivates enhancer response element–containing genes and can induce LTF in the absence of CRE- and CREB-mediated gene expression. Collectively, these results suggest that PKA-activated ApAF–ApC/EBP heterodimer is a core downstream effector of ApCREB in the consolidation of LTF.

2009 ◽  
Vol 89 (1) ◽  
pp. 121-145 ◽  
Author(s):  
Cristina M. Alberini

Transcription is a molecular requisite for long-term synaptic plasticity and long-term memory formation. Thus, in the last several years, one main interest of molecular neuroscience has been the identification of families of transcription factors that are involved in both of these processes. Transcription is a highly regulated process that involves the combined interaction and function of chromatin and many other proteins, some of which are essential for the basal process of transcription, while others control the selective activation or repression of specific genes. These regulated interactions ultimately allow a sophisticated response to multiple environmental conditions, as well as control of spatial and temporal differences in gene expression. Evidence based on correlative changes in expression, genetic mutations, and targeted molecular inhibition of gene expression have shed light on the function of transcription in both synaptic plasticity and memory formation. This review provides a brief overview of experimental work showing that several families of transcription factors, including CREB, C/EBP, Egr, AP-1, and Rel, have essential functions in both processes. The results of this work suggest that patterns of transcription regulation represent the molecular signatures of long-term synaptic changes and memory formation.


2005 ◽  
Vol 21 (10) ◽  
pp. 2845-2852 ◽  
Author(s):  
Ramiro Freudenthal ◽  
Mariano M. Boccia ◽  
Gabriela B. Acosta ◽  
Mariano G. Blake ◽  
Emiliano Merlo ◽  
...  

2008 ◽  
Vol 1 (1) ◽  
pp. 3 ◽  
Author(s):  
Yong-Seok Lee ◽  
Craig H Bailey ◽  
Eric R Kandel ◽  
Bong-Kiun Kaang

2012 ◽  
Vol 2 (11) ◽  
pp. 1437-1445 ◽  
Author(s):  
Ari Winbush ◽  
Danielle Reed ◽  
Peter L. Chang ◽  
Sergey V. Nuzhdin ◽  
Lisa C. Lyons ◽  
...  

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Snehajyoti Chatterjee ◽  
Christopher C. Angelakos ◽  
Ethan Bahl ◽  
Joshua D. Hawk ◽  
Marie E. Gaine ◽  
...  

Abstract Background CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors potentially affecting expression of thousands of genes. Identifying specific domain functions for multi-domain proteins is essential to understand processes such as cognitive function and circadian clocks. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. Results We found that CBPKIX/KIX mice were impaired in long-term memory, but not learning acquisition or short-term memory for the Morris water maze. Using an unbiased analysis of gene expression in the dorsal hippocampus after training in the Morris water maze or contextual fear conditioning, we discovered dysregulation of CREB, CLOCK, and BMAL1 target genes and downregulation of circadian genes in CBPKIX/KIX mice. Given our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity and phase resetting in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark. Interestingly, CBPKIX/KIX mice displayed phase delays and advances in response to photic stimulation comparable to wildtype littermates. Thus, this work delineates site-specific regulation of the circadian clock by a multi-domain protein. Conclusions These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms. Graphical abstract


Cell ◽  
2002 ◽  
Vol 111 (4) ◽  
pp. 483-493 ◽  
Author(s):  
Zhonghui Guan ◽  
Maurizio Giustetto ◽  
Stavros Lomvardas ◽  
Joung-Hun Kim ◽  
Maria Concetta Miniaci ◽  
...  

1992 ◽  
Vol 119 (5) ◽  
pp. 1069-1076 ◽  
Author(s):  
D Kuhl ◽  
T E Kennedy ◽  
A Barzilai ◽  
E R Kandel

Long-term memory for sensitization of the gill- and siphon-withdrawal reflexes in Aplysia californica requires RNA and protein synthesis. These long-term behavioral changes are accompanied by long-term facilitation of the synaptic connections between the gill and siphon sensory and motor neurons, which are similarly dependent on transcription and translation. In addition to showing an increase in over-all protein synthesis, long-term facilitation is associated with changes in the expression of specific early, intermediate, and late proteins, and with the growth of new synaptic connections between the sensory and motor neurons of the reflex. We previously focused on early proteins and have identified four proteins as members of the immunoglobulin family of cell adhesion molecules related to NCAM and fasciclin II. We have now cloned the cDNA corresponding to one of the late proteins, and identified it as the Aplysia homolog of BiP, an ER resident protein involved in the folding and assembly of secretory and membrane proteins. Behavioral training increases the steady-state level of BiP mRNA in the sensory neurons. The increase in the synthesis of BiP protein is first detected 3 h after the onset of facilitation, when the increase in overall protein synthesis reaches its peak and the formation of new synaptic terminals becomes apparent. These findings suggest that the chaperon function of BiP might serve to fold proteins and assemble protein complexes necessary for the structural changes characteristic of long-term memory.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Vivek Sagar ◽  
Thorsten Kahnt

Memorable positive and negative experiences produce different profiles of gene expression in brain areas associated with long-term memory.


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