Document Detail

AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila.
MedLine Citation:
PMID:  11976688     Owner:  NLM     Status:  MEDLINE    
Activity-regulated gene expression mediates many aspects of neural plasticity, including long-term memory. In the prevailing view, patterned synaptic activity causes kinase-mediated activation of the transcription factor cyclic AMP response-element-binding protein, CREB. Together with appropriate cofactors, CREB then transcriptionally induces a group of 'immediate early' transcription factors and, eventually, effector proteins that establish or consolidate synaptic change. Here, using a Drosophila model synapse, we analyse cellular functions and regulation of the best known immediate early transcription factor, AP-1; a heterodimer of the basic leucine zipper proteins Fos and Jun. We observe that AP-1 positively regulates both synaptic strength and synapse number, thus showing a greater range of influence than CREB. Observations from genetic epistasis and RNA quantification experiments indicate that AP-1 acts upstream of CREB, regulates levels of CREB messenger RNA, and functions at the top of the hierarchy of transcription factors known to regulate long-term plasticity. A Jun-kinase signalling module provides a CREB-independent route for neuronal AP-1 activation; thus, CREB regulation of AP-1 expression may, in some neurons, constitute a positive feedback loop rather than the primary step in AP-1 activation.
Subhabrata Sanyal; David J Sandstrom; Charles A Hoeffer; Mani Ramaswami
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature     Volume:  416     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-26     Completed Date:  2002-05-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  870-4     Citation Subset:  IM    
Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721, USA.
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MeSH Terms
Cell Count
Cyclic AMP / metabolism
Cyclic AMP Response Element-Binding Protein / metabolism*
Drosophila melanogaster / genetics*,  growth & development,  metabolism*
Epistasis, Genetic
Gene Expression Regulation, Developmental*
JNK Mitogen-Activated Protein Kinases
Larva / genetics,  growth & development,  metabolism
Mitogen-Activated Protein Kinases / metabolism
Neuromuscular Junction / cytology,  enzymology,  growth & development,  metabolism
Neuronal Plasticity*
Promoter Regions, Genetic / genetics
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
RNA, Messenger / genetics,  metabolism
Signal Transduction
Synapses / enzymology,  metabolism*
Transcription Factor AP-1 / metabolism*
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Transcription Factor AP-1; 60-92-4/Cyclic AMP; EC Mitogen-Activated Protein Kinases; EC Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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