AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila. Journal Article uri icon



  • 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.

publication date

  • April 25, 2002

has subject area

has restriction

  • closed

Date in CU Experts

  • September 9, 2013 10:43 AM

Full Author List

  • Sanyal S; Sandstrom DJ; Hoeffer CA; Ramaswami M

author count

  • 4

published in

Other Profiles

International Standard Serial Number (ISSN)

  • 0028-0836

Additional Document Info

start page

  • 870

end page

  • 874


  • 416


  • 6883