RETRACTED: Imaging Activity-Dependent Regulation of Neurexin-Neuroligin Interactions Using trans-Synaptic Enzymatic Biotinylation
Open accessAbstract
The functions of trans-synaptic adhesion molecules, such as neurexin and neuroligin, have been difficult to study due to the lack of methods to directly detect their binding in living neurons. Here, we use biotin labeling of intercellular contacts (BLINC), a method for imaging protein interactions based on interaction-dependent biotinylation of a peptide by E. coli biotin ligase, to visualize neurexin-neuroligin trans-interactions at synapses and study their role in synapse development. We found that both developmental maturation and acute synaptic activity stimulate the growth of neurexin-neuroligin adhesion complexes via a combination of neurexin and neuroligin surface insertion and internalization arrest. Both mechanisms require NMDA receptor activity. We also discovered that disruption of activity-induced neurexin-neuroligin complex growth prevents recruitment of the AMPA receptor, a hallmark of mature synapses. Our results provide support for neurexin-neuroligin function in synapse maturation and introduce a general method to study intercellular protein-protein interactions.
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The interaction between neurexins and neuroligins is regulated by neuronal activity, providing further evidence that mutations causing ASD might disrupt activity-dependent processes controlling synaptic function.
“The interaction between neurexins and neuroligins is regulated by neuronal activity, providing further evidence that mutations that cause ASD might be disrupting activity-dependent processes that control synaptic function.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [44]
Neuronal activity induces insertion of neurexin and neuroligin into the synaptic membrane and suppresses their internalization, leading to an overall increase in trans-synaptic neurexin-neuroligin interaction.
“Neuronal activity induced both the insertion of neurexin and neuroligin into the synaptic membrane and suppressed internalization of neurexin and neuroligin from the synaptic membrane, leading to an overall increase in the trans-synaptic neurexin–neuroligin interaction.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [44]
Disruption of this activity-regulated enhancement impaired recruitment of AMPA receptors to the synaptic membrane, altering synaptic function.
“Disruption of this activity-regulated enhancement impaired the recruitment of AMPA receptors to the synaptic membrane, thereby altering synaptic function44.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [44]
Neuronal activity acutely promotes an increase in the interaction of neurexins and neuroligins across the synapse in an NMDA-receptor-dependent manner.
“Using this approach, neuronal activity was found to acutely promote an increase in the interaction of neurexins and neuroligins across the synapse in an NMDA-receptor-dependent manner44.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [44]
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- Authors
- Thyagarajan, A., & Ting, A. Y.
- Affiliations
- Massachusetts Institute of Technology (US)
- ORCID
- Ting, Alice Y.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 143
- Issue
- 3
- Pages
- 456-469
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2966532
- OpenAlex
- W2080007501
- Cited by
- 35
- References
- 44
- Citations by year
- 2018: 2 · 2015: 1 · 2014: 3 · 2013: 7 · 2012: 8
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Autism Speaks (AS4813)
- National Institutes of Health (DP1OD003961)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
- Keywords
- neurexin, neuroligins, synapse maturation, synaptic activity, NMDA receptor, retracted article
- MeSH terms
- Animals, Microscopy, Fluorescence, Nerve Tissue Proteins, Neurons, Repressor Proteins, Synapses, Cell Adhesion Molecules, Neuronal, Rats, Sprague-Dawley, Carbon-Nitrogen Ligases, Biotinylation, Escherichia coli Proteins, Rats
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