Presynaptic Terminals Independently Regulate Synaptic Clustering and Autophagy of GABAAReceptors in Caenorhabditis elegans
Open accessAbstract
Synaptic clustering of GABAA receptors is important for the function of inhibitory synapses, influencing synapse strength and, consequently, the balance of excitation and inhibition in the brain. Presynaptic terminals are known to induce GABAA receptor clustering during synaptogenesis, but the mechanisms of cluster formation and maintenance are not known. To study how presynaptic neurons direct the formation of GABAA receptor clusters, we have investigated GABAA receptor localization in postsynaptic cells that fail to receive presynaptic contacts in Caenorhabditis elegans. Postsynaptic muscles in C. elegans receive acetylcholine and GABA motor innervation, and GABAA receptors cluster opposite GABA terminals. Selective loss of GABA inputs caused GABAA receptors to be diffusely distributed at or near the muscle cell surface, confirming that GABA presynaptic terminals induce GABAA receptor clustering. In contrast, selective loss of acetylcholine innervation had no effect on GABAA receptor localization. However, loss of both GABA and acetylcholine inputs together caused GABAA receptors to traffic to intracellular autophagosomes. Autophagosomes normally transport bulk cytoplasm to the lysosome for degradation. However, we show that GABAA receptors traffic to autophagosomes after endocytic removal from the cell surface and that acetylcholine receptors in the same cells do not traffic to autophagosomes. Thus, autophagy can degrade cell-surface receptors and can do so selectively. Our results show that presynaptic terminals induce GABAA receptor clustering by independently controlling synaptic localization and surface stability of GABAA receptors. They also demonstrate a novel function for autophagy in GABAA receptor degradative trafficking.
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Autophagy may remodel dendritic spines by directing internalized postsynaptic membrane neurotransmitter receptors, including GABA-A and AMPAR, toward lysosomal degradation.
“Autophagy may remodel dendritic spines by directing internalized postsynaptic membrane neurotransmitter receptors, including GABA-A (Rowland et al., 2006) and AMPAR (Shehata et al., 2012), toward lysosomal degradation.”
From Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits (2014) · cites this paper as Rowland et al., 2006
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- Authors
- Rowland, A. M., Richmond, J. E., Olsen, J. G., Hall, D. H., & Bamber, B. A.
- Affiliations
- University of Utah (US)
- Albert Einstein College of Medicine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-02-08
- Volume
- 26
- Issue
- 6
- Pages
- 1711-1720
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6793639
- OpenAlex
- W2066358591
- Cited by
- 159
- References
- 61
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 12 · 2020: 15 · 2019: 14 · 2018: 11 · 2017: 8 · 2016: 6 · 2015: 5 · 2014: 9 · 2013: 5 · 2012: 13
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Whitehall Foundation
- National Institutes of Health (1r21mh064699-01, R24OD010943)
- National Institute of Mental Health (MH64699)
- National Institute of General Medical Sciences (GM007464, T32GM007464)
- National Institute of Neurological Disorders and Stroke (NS43345, R01NS043345, R01NS041477, NS041477)
- National Center for Research Resources (RR12596, R24RR012596)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- GABAA receptor, synaptic clustering, presynaptic terminals, autophagy, autophagosomes, receptor degradation, Caenorhabditis elegans, inhibitory synapses, acetylcholine receptor, receptor trafficking, synaptogenesis, excitation-inhibition balance
- MeSH terms
- Animals, Autophagy, Axons, Motor Neurons, Neuromuscular Junction, Receptors, GABA-A, Synapses, Transfection, Caenorhabditis elegans, Presynaptic Terminals, Genes, Reporter
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