CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation.
Although CREB seems to be important for memory formation, it is not known which of the isoforms of CREB, CREM, or ATF1 are expressed in the neurons that undergo long-term synaptic changes and what roles they have in memory formation. We have found a single Aplysia CREB1 gene homologous to both mammalian CREB and CREM and have characterized in the sensory neurons that mediate gill-withdrawal reflex the expression and function of the three proteins that it encodes: CREB1a, CREB1b, and CREB1c. CREB1a is a transcriptional activator that is both necessary and, upon phosphorylation, sufficient for long-term facilitation. CREB1b is a repressor of long-term facilitation. Cytoplasmic CREB1c modulates both the short- and long-term facilitation. Thus, in the sensory neurons, CREB1 encodes a critical regulatory unit converting short- to long-term synaptic changes.
Bartsch
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Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University and New York State Psychiatric Institute, New York 10032, USA. db57@columbia.edu
Casadio
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A
Karl
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Serodio
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P
Kandel
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ER
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D001483:Base Sequence; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008322:Mammals; D008568:Memory / Q000502:physiology*; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000502:physiology*; D013569:Synapses / Q000737:chemistry / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases