Sequestration of cAMP response element-binding proteins by transcription factor decoys causes collateral elaboration of regenerating Aplysia motor neuron axons.
Axonal injury increases intracellular Ca2+ and cAMP and has been shown to induce gene expression, which is thought to be a key event for regeneration. Increases in intracellular Ca2+ and/or cAMP can alter gene expression via activation of a family of transcription factors that bind to and modulate the expression of CRE (Ca2+/cAMP response element) sequence-containing genes. We have used Aplysia motor neurons to examine the role of CRE-binding proteins in axonal regeneration after injury. We report that axonal injury increases the binding of proteins to a CRE sequence-containing probe. In addition, Western blot analysis revealed that the level of ApCREB2, a CRE sequence-binding repressor, was enhanced as a result of axonal injury. The sequestration of CRE-binding proteins by microinjection of CRE sequence-containing plasmids enhanced axon collateral formation (both number and length) as compared with control plasmid injections. These findings show that Ca2+/cAMP-mediated gene expression via CRE-binding transcription factors participates in the regeneration of motor neuron axons.
Dash
P K
PK
Department of Neurobiology and Anatomy, University of Texas-Houston Health Science Center, Houston, TX 77225, USA. pdash@nba19.med.uth.tmc.edu
Tian
L M
LM
Moore
A N
AN
D000818:Animals; D001048:Aplysia; D001369:Axons / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D000242:Cyclic AMP; D002118:Calcium