The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons
Open accessAbstract
Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.
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Cites
Mitochondria as sensors and regulators of calcium signalling
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Neuroligin Expressed in Nonneuronal Cells Triggers Presynaptic Development in Contacting Axons
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Differential signaling via the same axon of neocortical pyramidal neurons
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Target-cell-specific facilitation and depression in neocortical circuits
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“In addition, the same pyramidal neurons in the neocortex have target cell-specific neurotransmitter release properties [9,11,12].”
BackgroundKang, J.-S., Tian, J.-H., Pan, P.-Y., Zald, P., Li, C., Deng, C., & Sheng, Z.-H. (2008) · Cell · doi:10.1016/j.cell.2007.11.024 · Cited by 598
Short-Term Presynaptic Plasticity
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Molecular Mechanisms for Synchronous, Asynchronous, and Spontaneous Neurotransmitter Release
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Liang, G., & Bushman, F. D. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00536-5 · Cited by 624
Mitochondria at the neuronal presynapse in health and disease
Devine, M. J., & Kittler, J. T. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.170 · Cited by 615
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Fišer, C., Robinson, C. T., & Malard, F. (2018) · Molecular Ecology · doi:10.1111/mec.14486 · Cited by 574
Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration
Verma, M., Lizama, B. N., & Chu, C. T. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-021-00278-7 · Cited by 451
Lewis, T. L., Kwon, S.-K., Lee, A., Shaw, R., & Polleux, F. (2018) · Nature Communications · doi:10.1038/s41467-018-07416-2 · Cited by 260
Self-citation
Metadata
- Authors
- Kwon, S.-K., Sando, R., Lewis, T. L., Hirabayashi, Y., Maximov, A., & Polleux, F.
- Venue
- PLOS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-07-18
- Volume
- 14
- Issue
- 7
- Pages
- e1002516
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2493737149
- Cited by
- 200
- References
- 18
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- gold
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- Kwon, S.-K., Sando, R., Lewis, T. L., Hirabayashi, Y., Maximov, A., & Polleux, F. (2016). LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons. PLOS Biology. https://doi.org/10.1371/journal.pbio.1002516
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