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Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster

Abstract

Synaptic stimulation activates signal transduction pathways, producing persistently active protein kinases. PKMζ is a truncated, persistently active isoform of atypical protein kinase C-ζ (aPKCζ), which lacks the N-terminal pseudosubstrate regulatory domain. Using a Pavlovian olfactory learning task in Drosophila, we found that induction of the mouse aPKMζ (MaPKMζ) 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 MaPKCζ (DaPKM) was present and active in fly heads. Chelerythrine, an inhibitor of PKMζ, and the induction of a dominant-negative MaPKMζ 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.

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Figure 1: Memory enhancement by MaPKMζ in Drosophila.
Figure 2: Memory enhancement requires persistent kinase activity and is not due to sensory enhancement.
Figure 3: Expression and biochemical analyses of transgenic lines.
Figure 4: MaPKMζ induction enhances 4-day memory after massed, but not spaced training.
Figure 5: MaPKMζ induction corrects the memory deficit of radish mutants.
Figure 6: A Drosophila homolog of MaPKMζ is present and active in Drosophila head extracts.
Figure 7: Chelerythrine treatment or KI-MaPKMζ expression inhibits 24-h memory produced by massed training, but not learning, in Drosophila.
Figure 8: DaPKM induction enhances memory.

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Acknowledgements

E.A.D. is a postdoctoral fellow (fellowship no. PF-99-342-01-DDC) of the American Cancer Society. M.K.T. is a Fulbright/CONACYT fellow. A. Romanelli and J. Blenis provided the K281W mutant clone. We thank K. Svoboda, J. Dubnau and members of the Yin and Tully laboratories for comments on the manuscript.

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Correspondence to Jerry C.P. Yin.

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Drier, E., Tello, M., Cowan, M. et al. Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster. Nat Neurosci 5, 316–324 (2002). https://doi.org/10.1038/nn820

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