title: CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation.
abstract: 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.
authors.affiliation: 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
authors.forename: D
authors.initials: D
authors.lastname: Bartsch
authors.forename: A
authors.initials: A
authors.lastname: Casadio
authors.forename: K A
authors.initials: KA
authors.lastname: Karl
authors.forename: P
authors.initials: P
authors.lastname: Serodio
authors.forename: E R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: 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*
chemical_list: 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