Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster.
Synaptic stimulation activates signal transduction pathways, producing persistently active protein kinases. PKMzeta is a truncated, persistently active isoform of atypical protein kinase C-zeta (aPKCzeta), which lacks the N-terminal pseudosubstrate regulatory domain. Using a Pavlovian olfactory learning task in Drosophila, we found that induction of the mouse aPKMzeta (MaPKMzeta) transgene enhanced memory. The enhancement required persistent kinase activity and was temporally specific, with optimal induction at 30 minutes after training. Induction also enhanced memory after massed training and corrected the memory defect of radish mutants, but did not improve memory produced by spaced training. The 'M' isoform of the Drosophila homolog of MaPKCzeta (DaPKM) was present and active in fly heads. Chelerythrine, an inhibitor of PKMzeta, and the induction of a dominant-negative MaPKMzeta transgene inhibited memory without affecting learning. Finally, induction of DaPKM after training also enhanced memory. These results show that atypical PKM is sufficient to enhance memory in Drosophila and suggest that it is necessary for normal memory maintenance.
Drier
Eric A
EA
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Tello
Marcela K
MK
Cowan
Maureen
M
Wu
Priscilla
P
Blace
Nancy
N
Sacktor
Todd Charlton
TC
Yin
Jerry C P
JC
D000470:Alkaloids; D000818:Animals; D030801:Animals, Genetically Modified; D001362:Avoidance Learning; D053119:Benzophenanthridines; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006257:Head / Q000502:physiology; D006358:Hot Temperature; D008297:Male; D008568:Memory / Q000502:physiology*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012903:Smell / Q000502:physiology; D014020:Tissue Extracts / Q000737:chemistry / Q000378:metabolism
D000470:Alkaloids; D053119:Benzophenanthridines; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D014020:Tissue Extracts; C016299:chelerythrine; D011493:Protein Kinase C