Poly-(ADP-ribose) polymerase-1 is necessary for long-term facilitation in Aplysia.
Activity-dependent long-term synaptic plasticity requires gene expression and protein synthesis. Identifying essential genes and studying their transcriptional and translational regulation are key steps to understanding how synaptic changes become long lasting. Recently, the enzyme poly-(ADP-ribose) polymerase 1 (PARP-1) was shown to be necessary for long-term memory (LTM) in Aplysia. Since PARP-1 decondenses chromatin, we hypothesize that this enzyme regulates the expression of specific genes essential for long-term synaptic plasticity that underlies LTM. We cloned Aplysia PARP-1 (ApPARP-1) and determined that its expression in sensory neurons is necessary for serotonin (5-HT)-mediated long-term facilitation (LTF) of sensorimotor neuron synapses. PARP enzymatic activity is also required, since transient application of PARP inhibitors blocked LTF. Differential display and RNA analysis of ganglia dissected from intact animals exposed to 5-HT identified the ribosomal RNA genes as PARP-dependent effector genes. The increase in the expression of rRNAs is long lasting and dynamic. Pulse-labeling RNA studies showed a PARP-dependent increase in rRNAs but not in the total RNA 24 h after 5-HT treatment. Moreover, the expression of both the AprpL27a (Aplysia ribosomal protein L27a) and the ApE2N (Aplysia ubiquitin-conjugating enzyme E2N) mRNAs also increased after 5-HT. Thus, our results suggest that 5-HT, in part by regulating PARP-1 activity, alters the expression of transcripts required for the synthesis of new ribosomes necessary for LTF.
Hernández
A Iván
AI
Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York, New York 10032, USA. ivan.hernandez@downstate.edu
Wolk
Jason
J
Hu
Jiang-Yuan
JY
Liu
Jinming
J
Kurosu
Takeshi
T
Schwartz
James H
JH
Schacher
Samuel
S
D000818:Animals; D001048:Aplysia; D001483:Base Sequence; D001549:Benzamides / Q000008:administration & dosage; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D010616:Phenanthrenes / Q000008:administration & dosage; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D013997:Time Factors; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
D001549:Benzamides; D004791:Enzyme Inhibitors; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; C034661:ribosomal proteins L27; D012701:Serotonin; C025160:3-aminobenzamide; D044763:Ubiquitin-Conjugating Enzymes; D011065:Poly(ADP-ribose) Polymerases