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Synaptic Orb2A Bridges Memory Acquisition and Late Memory Consolidation in Drosophila.

Krüttner S, Traunmüller L, Dag U, Jandrasits K, Stepien B, Iyer N, Fradkin LG, Noordermeer JN, Mensh BD, Keleman K - Cell Rep (2015)

Bottom Line: Furthermore, we present evidence that, during learning, the translational regulator Orb2A tags specific synapses of mushroom body neurons for later consolidation.Consolidation involves the subsequent recruitment of Orb2B and the activity-dependent synthesis of CaMKII.Thus, our results provide evidence for the role of a neuromodulated, synapse-restricted molecule bridging memory acquisition and long-term memory consolidation in a learning animal.

View Article: PubMed Central - PubMed

Affiliation: Research Institute of Molecular Pathology, Doktor Bohr Gasse 7, A-1030 Vienna, Austria; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.

No MeSH data available.


Related in: MedlinePlus

Orb2 Regulates Synthesis of CaMKII in MB Neurons(A) Orb2 regulates translation of CaMKII through its 3′ UTR. Translation of the Firefly luciferase (Fluc) reporter tethered to the CaMKII 3′ UTR is suppressed by Orb2, but not when tethered to the control 3′ UTR, which does not contain Orb2-specific binding sequence. The values on y axis represent the ratio of the normalized Fluc to Rluc fluorescence in the presence of wt Orb2 to the Fluc/Rluc fluorescence in the presence of Orb2RBD∗ with RBD mutated. ∗p < 0.05. See Table S11.(B) Representative confocal projections of the MB (lobes) expressing UAS-EYFP-CaMKII-3′UTR with the MB247-Gal4 and stained with the anti-GFP antibodies. The adult brains were either unstimulated (left panel) or stimulated (right panel) by feeding with dopamine.(C) UAS-EYFP-CaMKII-3′UTR was expressed in the MB neurons with the MB247-Gal4. Intensity of fluorescence was measured in the MB γ lobe of the adult brains either wild-type (orb2+; left panel) or orb2 mutant (orb2ΔA; right panel) stimulated by feeding with dopamine at the indicated time intervals. p values are for H0 ftx = ft0. See Table S12.
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fig7: Orb2 Regulates Synthesis of CaMKII in MB Neurons(A) Orb2 regulates translation of CaMKII through its 3′ UTR. Translation of the Firefly luciferase (Fluc) reporter tethered to the CaMKII 3′ UTR is suppressed by Orb2, but not when tethered to the control 3′ UTR, which does not contain Orb2-specific binding sequence. The values on y axis represent the ratio of the normalized Fluc to Rluc fluorescence in the presence of wt Orb2 to the Fluc/Rluc fluorescence in the presence of Orb2RBD∗ with RBD mutated. ∗p < 0.05. See Table S11.(B) Representative confocal projections of the MB (lobes) expressing UAS-EYFP-CaMKII-3′UTR with the MB247-Gal4 and stained with the anti-GFP antibodies. The adult brains were either unstimulated (left panel) or stimulated (right panel) by feeding with dopamine.(C) UAS-EYFP-CaMKII-3′UTR was expressed in the MB neurons with the MB247-Gal4. Intensity of fluorescence was measured in the MB γ lobe of the adult brains either wild-type (orb2+; left panel) or orb2 mutant (orb2ΔA; right panel) stimulated by feeding with dopamine at the indicated time intervals. p values are for H0 ftx = ft0. See Table S12.

Mentions: Dopamine regulates the expression of proteins essential for long-lasting memories (Berke et al., 1998), such as calcium/calmodulin-dependent kinase (CaMKII). CaMKII translation at synapses is dependent on neuronal activity both in mouse and Drosophila (Ashraf et al., 2006; Coultrap and Bayer, 2012) and is conferred by its 3′ UTR, which is recognized by CPEB proteins in mouse (Wu et al., 1998). Drosophila CaMKII has been identified as an Orb2 mRNA target (our unpublished results), and Orb2 regulates its translation by binding to the specific sequence in the 3′ UTR (Figure 7A; Table S11).


Synaptic Orb2A Bridges Memory Acquisition and Late Memory Consolidation in Drosophila.

Krüttner S, Traunmüller L, Dag U, Jandrasits K, Stepien B, Iyer N, Fradkin LG, Noordermeer JN, Mensh BD, Keleman K - Cell Rep (2015)

Orb2 Regulates Synthesis of CaMKII in MB Neurons(A) Orb2 regulates translation of CaMKII through its 3′ UTR. Translation of the Firefly luciferase (Fluc) reporter tethered to the CaMKII 3′ UTR is suppressed by Orb2, but not when tethered to the control 3′ UTR, which does not contain Orb2-specific binding sequence. The values on y axis represent the ratio of the normalized Fluc to Rluc fluorescence in the presence of wt Orb2 to the Fluc/Rluc fluorescence in the presence of Orb2RBD∗ with RBD mutated. ∗p < 0.05. See Table S11.(B) Representative confocal projections of the MB (lobes) expressing UAS-EYFP-CaMKII-3′UTR with the MB247-Gal4 and stained with the anti-GFP antibodies. The adult brains were either unstimulated (left panel) or stimulated (right panel) by feeding with dopamine.(C) UAS-EYFP-CaMKII-3′UTR was expressed in the MB neurons with the MB247-Gal4. Intensity of fluorescence was measured in the MB γ lobe of the adult brains either wild-type (orb2+; left panel) or orb2 mutant (orb2ΔA; right panel) stimulated by feeding with dopamine at the indicated time intervals. p values are for H0 ftx = ft0. See Table S12.
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Related In: Results  -  Collection

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fig7: Orb2 Regulates Synthesis of CaMKII in MB Neurons(A) Orb2 regulates translation of CaMKII through its 3′ UTR. Translation of the Firefly luciferase (Fluc) reporter tethered to the CaMKII 3′ UTR is suppressed by Orb2, but not when tethered to the control 3′ UTR, which does not contain Orb2-specific binding sequence. The values on y axis represent the ratio of the normalized Fluc to Rluc fluorescence in the presence of wt Orb2 to the Fluc/Rluc fluorescence in the presence of Orb2RBD∗ with RBD mutated. ∗p < 0.05. See Table S11.(B) Representative confocal projections of the MB (lobes) expressing UAS-EYFP-CaMKII-3′UTR with the MB247-Gal4 and stained with the anti-GFP antibodies. The adult brains were either unstimulated (left panel) or stimulated (right panel) by feeding with dopamine.(C) UAS-EYFP-CaMKII-3′UTR was expressed in the MB neurons with the MB247-Gal4. Intensity of fluorescence was measured in the MB γ lobe of the adult brains either wild-type (orb2+; left panel) or orb2 mutant (orb2ΔA; right panel) stimulated by feeding with dopamine at the indicated time intervals. p values are for H0 ftx = ft0. See Table S12.
Mentions: Dopamine regulates the expression of proteins essential for long-lasting memories (Berke et al., 1998), such as calcium/calmodulin-dependent kinase (CaMKII). CaMKII translation at synapses is dependent on neuronal activity both in mouse and Drosophila (Ashraf et al., 2006; Coultrap and Bayer, 2012) and is conferred by its 3′ UTR, which is recognized by CPEB proteins in mouse (Wu et al., 1998). Drosophila CaMKII has been identified as an Orb2 mRNA target (our unpublished results), and Orb2 regulates its translation by binding to the specific sequence in the 3′ UTR (Figure 7A; Table S11).

Bottom Line: Furthermore, we present evidence that, during learning, the translational regulator Orb2A tags specific synapses of mushroom body neurons for later consolidation.Consolidation involves the subsequent recruitment of Orb2B and the activity-dependent synthesis of CaMKII.Thus, our results provide evidence for the role of a neuromodulated, synapse-restricted molecule bridging memory acquisition and long-term memory consolidation in a learning animal.

View Article: PubMed Central - PubMed

Affiliation: Research Institute of Molecular Pathology, Doktor Bohr Gasse 7, A-1030 Vienna, Austria; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.

No MeSH data available.


Related in: MedlinePlus