A high-efficiency protein transduction system demonstrating the role of PKA in long-lasting long-term potentiation
- PMID: 11487623
- PMCID: PMC6763134
- DOI: 10.1523/JNEUROSCI.21-16-06000.2001
A high-efficiency protein transduction system demonstrating the role of PKA in long-lasting long-term potentiation
Abstract
Proteins and peptides have been demonstrated to penetrate across the plasma membrane of eukaryotic cells by protein transduction domains. We show that protein transduction by 11 arginine (11R) is an efficient method of delivering proteins into the neurons of brain slices. Here, we demonstrate that PKA inhibitory peptide, fused with 11R and nuclear localization signal, delivers the peptide exclusively into the nuclear compartment of neurons in brain slices. This inhibitory peptide blocked both cAMP responsive element-binding protein phosphorylation and long-lasting long-term potentiation (LTP) induction, but not early LTP. These results highlight transduction of proteins and peptides into specific neuronal subcellular compartments in brain slices as a powerful tool for studying neuronal plasticity.
Figures
![Fig. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6763134/bin/ns1615487001.gif)
![Fig. 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6763134/bin/ns1615487002.gif)
![Fig. 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6763134/bin/ns1615487003.gif)
![Fig. 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6763134/bin/ns1515487004.gif)
![Fig. 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6763134/bin/ns1615487005.gif)
![Fig. 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6763134/bin/ns1515487006.gif)
![Fig. 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6763134/bin/ns1615487007.gif)
Similar articles
-
Single cell analysis of activity-dependent cyclic AMP-responsive element-binding protein phosphorylation during long-lasting long-term potentiation in area CA1 of mature rat hippocampal-organotypic cultures.Neuroscience. 2005;131(3):601-10. doi: 10.1016/j.neuroscience.2004.12.002. Neuroscience. 2005. PMID: 15730866
-
Protein Therapy: in vivo protein transduction by polyarginine (11R) PTD and subcellular targeting delivery.Curr Protein Pept Sci. 2003 Apr;4(2):151-7. doi: 10.2174/1389203033487270. Curr Protein Pept Sci. 2003. PMID: 12678854 Review.
-
Postsynaptic application of a peptide inhibitor of cAMP-dependent protein kinase blocks expression of long-lasting synaptic potentiation in hippocampal neurons.J Neurosci. 2003 Feb 15;23(4):1142-50. doi: 10.1523/JNEUROSCI.23-04-01142.2003. J Neurosci. 2003. PMID: 12598602 Free PMC article.
-
An extranuclear locus of cAMP-dependent protein kinase action is necessary and sufficient for promotion of spiral ganglion neuronal survival by cAMP.J Neurosci. 2003 Feb 1;23(3):777-87. doi: 10.1523/JNEUROSCI.23-03-00777.2003. J Neurosci. 2003. PMID: 12574406 Free PMC article.
-
Genetic and pharmacological demonstration of differential recruitment of cAMP-dependent protein kinases by synaptic activity.J Neurophysiol. 2000 Dec;84(6):2739-45. doi: 10.1152/jn.2000.84.6.2739. J Neurophysiol. 2000. PMID: 11110804
Cited by
-
Dynamics and Mechanisms of ERK Activation after Different Protocols that Induce Long-Term Synaptic Facilitation in Aplysia.Oxf Open Neurosci. 2022 Oct 18;2:kvac014. doi: 10.1093/oons/kvac014. eCollection 2023. Oxf Open Neurosci. 2022. PMID: 37649778 Free PMC article.
-
Arginine-Rich Cell-Penetrating Peptide-Mediated Transduction of Mouse Nasal Cells with FOXP3 Protein Alleviates Allergic Rhinitis.Pharmaceutics. 2023 Jun 19;15(6):1770. doi: 10.3390/pharmaceutics15061770. Pharmaceutics. 2023. PMID: 37376217 Free PMC article.
-
Quantitative description of the interactions among kinase cascades underlying long-term plasticity of Aplysia sensory neurons.Sci Rep. 2021 Jul 22;11(1):14931. doi: 10.1038/s41598-021-94393-0. Sci Rep. 2021. PMID: 34294802 Free PMC article.
-
Comparing Theories for the Maintenance of Late LTP and Long-Term Memory: Computational Analysis of the Roles of Kinase Feedback Pathways and Synaptic Reactivation.Front Comput Neurosci. 2020 Dec 16;14:569349. doi: 10.3389/fncom.2020.569349. eCollection 2020. Front Comput Neurosci. 2020. PMID: 33390922 Free PMC article.
-
Protein Kinase Inhibitor Peptide as a Tool to Specifically Inhibit Protein Kinase A.Front Physiol. 2020 Nov 25;11:574030. doi: 10.3389/fphys.2020.574030. eCollection 2020. Front Physiol. 2020. PMID: 33324237 Free PMC article. Review.
References
-
- Abel T, Nguyen PV, Barad M, Deuel TA, Kandel ER, Bourtchouladze R. Genetic demonstration of a role for PKA in late phase of LTP and hippocampus-based long-term memory. Cell. 1997;88:615–626. - PubMed
-
- Bear MF, Malenka RC. Synaptic plasticity: LTP and LTD. Curr Opin Neurobiol. 1994;4:389–399. - PubMed
-
- Bito H, Deisseroth K, Tsien RW. CREB phosphorylation and dephosphorylation: a Ca2+ and stimulus duration-dependent switch for hippocampal gene expression. Cell. 1996;87:1203–1214. - PubMed
-
- Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361:31–39. - PubMed
-
- Bourne HR, Nicoll R. Molecular machines integrate coincident synaptic signal. Cell. 1993;72:65–75. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources