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Activity- and mTOR-Dependent Suppression of Kv1.1 Channel mRNA Translation in Dendrites
Abstract
Mammalian target of rapamycin (mTOR) is implicated in synaptic plasticity and local translation in dendrites. We found that the mTOR inhibitor, rapamycin, increased the Kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted Kv1.1 surface expression on dendrites without altering its axonal expression. Moreover, endogenous Kv1.1 mRNA was detected in dendrites. Using Kv1.1 fused to the photoconvertible fluorescence protein Kaede as a reporter for local synthesis, we observed Kv1.1 synthesis in dendrites upon inhibition of mTOR or the N-methyl-d-aspartate (NMDA) glutamate receptor. Thus, synaptic excitation may cause local suppression of dendritic Kv1 channels by reducing their local synthesis.
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In the citing paper
“Pharmacological antagonism of N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptors that lies upstream of mTOR activation, promotes the synthesis of the voltage-gated potassium channel, Kv1.1, in dendrites (34,35).”
In the citing paper
“As expected, Kv1.1 protein (Kcna1) was only detected in the soluble fraction when mTORC1 was repressed, confirming our previous findings (31,34,35).”
In the citing paper
“Emerging data, however, show that suppressing mTORC1 activation can trigger local translation in neurons (34,35).”
In the citing paper
“Having previously shown in cultures that repression of mTORC1 by rapamycin increases Kv1.1 translation locally in dendrites, we present here that reduction of mTORC1 activity in vivo up-regulates protein expression in a region-specific manner (34).”
In the citing paper
“Given that some mRNAs are localized and translated locally within neurons (for example, [57,58]), an attractive possibility is that cell-type specific brain miRNAs regulate spatially localized translation of proteins.”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [57]
Citations
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Metadata
- Authors
- Raab-Graham, K. F., Haddick, P. C. G., Jan, Y. N., & Jan, L. Y.
- Affiliations
- Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California, San Francisco, CA 94158, USA.
- Howard Hughes Medical Institute (US)
- Corresponding author
- Haddick, Patrick C. G.
- Jan, Lily Yeh
- Venue
- Science
- Published
- 2006-10-06
- Volume
- 314
- Issue
- 5796
- Pages
- 144-148
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2028230396
- Cited by
- 267
- References
- 28
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 10 · 2022: 7 · 2021: 5 · 2020: 23 · 2019: 13 · 2018: 9 · 2017: 15 · 2016: 15 · 2015: 18 · 2014: 17 · 2013: 25 · 2012: 21
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f32mh013010-01)
- National Institute of Mental Health (MH13010, MH65334)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- Kv1.1, voltage-gated potassium channels, mTOR, local translation, dendrites, hippocampal neurons, rapamycin, NMDA receptor, synaptic plasticity, mRNA translation, channel surface expression, synaptic excitation
- MeSH terms
- Animals, Cells, Cultured, Dendrites, Hippocampus, Neuronal Plasticity, Neurons, Phosphorylation, Protein Kinases, Recombinant Fusion Proteins, RNA, Messenger, Sindbis Virus, Synapses, Protein Biosynthesis, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Excitatory Postsynaptic Potentials, Sirolimus, Oligonucleotide Array Sequence Analysis, 3' Untranslated Regions, Protein Kinase Inhibitors, Rats, Kv1.1 Potassium Channel, TOR Serine-Threonine Kinases, In Vitro Techniques
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