Enhancement of memory-related long-term facilitation by ApAF, a novel transcription factor that acts downstream from both CREB1 and CREB2.
The memory for sensitization of the gill withdrawal reflex in Aplysia is reflected in facilitation of the monosynaptic connection between the sensory and motor neurons of the reflex. The switch from short- to long-term facilitation requires activation of CREB1, derepression of ApCREB2, and induction of ApC/EBP. In search for genes that act downstream from CREB1, we have identified a transcription activator, ApAF, which is stimulated by protein kinase A and can dimerize with both ApC/EBP and ApCREB2. ApAF is necessary for long-term facilitation induced by five pulses of serotonin, by activation of CREB1, or by derepression of ApCREB2. Overexpression of ApAF enhances the long-term facilitation further. Thus, ApAF is a candidate memory enhancer gene downstream from both CREB1 and ApCREB2.
Bartsch
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D
Howard Hughes Medical Institute, Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University and New York State Psychiatric Institute, 722 West 168th Street New York, NY 10032, USA.
Ghirardi
M
M
Casadio
A
A
Giustetto
M
M
Karl
K A
KA
Zhu
H
H
Kandel
E R
ER
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D015723:Gene Library; D005880:Gills; D016350:Leucine Zippers; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000502:physiology; D011485:Protein Binding; D012018:Reflex; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*
C417672:ApAF protein, Aplysia; C097204:ApCREB2 protein, Aplysia californica; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases