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Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster
Eric A Drier1, Marcela K Tello, Maureen Cowan
1Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Abstract:
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.
Insights
Atypical protein kinase M (PKM) enhances memory formation in fruit flies. This protein kinase is sufficient to boost memory and appears necessary for maintaining normal memory processes.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Synaptic stimulation triggers signal transduction pathways, leading to persistently active protein kinases.
- PKMzeta is a persistently active isoform of atypical protein kinase C-zeta (aPKCzeta), lacking its N-terminal regulatory domain.
Purpose of the Study:
- To investigate the role of atypical protein kinase M (PKM) in memory formation and maintenance using Drosophila.
- To determine if PKMzeta is sufficient to enhance memory and if it is necessary for normal memory processes.
Main Methods:
- Utilized a Pavlovian olfactory learning task in Drosophila.
- Induced transgenes for mouse aPKMzeta (MaPKMzeta) and its Drosophila homolog (DaPKM).
- Administered PKMzeta inhibitor (chelerythrine) and a dominant-negative MaPKMzeta transgene.
Main Results:
- Induction of MaPKMzeta transgene enhanced memory, requiring persistent kinase activity and optimal at 30 minutes post-training.
- PKMzeta induction improved memory after massed training and rescued memory defects in radish mutants.
- PKMzeta inhibition and dominant-negative transgene expression impaired memory without affecting learning.
- Induction of DaPKM also enhanced memory, supporting PKM's role.
Conclusions:
- Atypical protein kinase M (PKM) is sufficient to enhance memory in Drosophila.
- PKM appears to be necessary for the normal maintenance of memory.