Ca2+-independent protein kinase C Apl II mediates the serotonin-induced facilitation at depressed aplysia sensorimotor synapses.
At nondepressed Aplysia sensory to motor synapses, serotonin (5-HT) facilitates transmitter release primarily through a protein kinase A pathway. In contrast, at depressed Aplysia sensory to motor synapses, 5-HT facilitates transmitter release primarily through a protein kinase C (PKC)-dependent pathway. It is known that only two phorbol ester-activated PKC isoforms, the Ca(2+)-dependent PKC Apl I and the Ca(2+)-independent PKC Apl II, exist in the Aplysia nervous system. For the first time, we have now been able to functionally determine which isoform of PKC is involved in a particular form of plasticity. We microinjected cultured sensorimotor pairs of neurons with various PKC constructs tagged with the enhanced green fluorescent protein as a reporter for successful plasmid expression. Our results demonstrate that short-term facilitation of depressed synapses is mediated by PKC Apl II. Dominant-negative PKC Apl II, but not dominant-negative PKC Apl I, disrupted the normal kinetics of 5-HT-induced facilitation by completely blocking its rapid onset. This effect was specific to depressed synapses, because dominant-negative PKC Apl II did not inhibit 5-HT-mediated facilitation of nondepressed synapses. Our results suggest that not only different signal transduction pathways but also different isoforms of a specific cascade may mediate physiological responses according to the state of a synapse.
Manseau
F
F
Laboratoire de Neurobiologie et Comportement, Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Université de Montréal, Montréal, Canada H3C 3J7.
Fan
X
X
Hueftlein
T
T
Sossin
W
W
Castellucci
V F
VF
D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005799:Genes, Dominant; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D007527:Isoenzymes / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics; D008845:Microinjections; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D014162:Transfection
D007527:Isoenzymes; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D012701:Serotonin; C121046:Apl II protein kinase C; D011493:Protein Kinase C; D002118:Calcium