Scribble Interacts with β-Catenin to Localize Synaptic Vesicles to Synapses
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An understanding of how synaptic vesicles are recruited to and maintained at presynaptic compartments is required to discern the molecular mechanisms underlying presynaptic assembly and plasticity. We have previously demonstrated that cadherin–β-catenin complexes cluster synaptic vesicles at presynaptic sites. Here we show that scribble interacts with the cadherin–β-catenin complex to coordinate vesicle localization. Scribble and β-catenin are colocalized at synapses and can be coimmunoprecipitated from neuronal lysates, indicating an interaction between scribble and β-catenin at the synapse. Using an RNA interference approach, we demonstrate that scribble is important for the clustering of synaptic vesicles at synapses. Indeed, in scribble knockdown cells, there is a diffuse distribution of synaptic vesicles along the axon, and a deficit in vesicle recycling. Despite this, synapse number and the distribution of the presynaptic active zone protein, bassoon, remain unchanged. These effects largely phenocopy those observed after ablation of β-catenin. In addition, we show that loss of β-catenin disrupts scribble localization in primary neurons but that the localization of β-catenin is not dependent on scribble. Our data supports a model by which scribble functions downstream of β-catenin to cluster synaptic vesicles at developing synapses.
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Scribble is an integral component of synaptic protein complexes and can coimmunoprecipitate with β-catenin, GIT1, β-PIX, and Neurexin.
“Scribble is an integral component of synaptic protein complexes and can coimmunoprecipitate with β-catenin, the ADP-ribosylation factor-1 GTPase-activating protein (GAP) GIT1, the Rac/Cdc42 guanine nucleotide exchange factor β-PIX, and transmembrane receptor Neurexin (Audebert et al., 2004; Sun et al., 2009; Sun and Bamji, 2011; Rui et al., 2017).”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Sun et al., 2009
Scribble coimmunoprecipitates with β-catenin, and Scribble synaptic localization is lost after β-catenin knockdown.
“Scribble coimmunoprecipitates with β-catenin, and Scribble synaptic localization is lost after β-catenin knockdown (Sun et al., 2009).”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Sun et al., 2009
Mouse Scribble is enriched at synapses of primary hippocampal neurons and in their spine precursors, where it colocalizes with the cadherin-catenin complex.
“Mouse Scribble is also enriched at synapses of primary hippocampal neurons (Sun et al., 2009) and in their “spine” precursors (Moreau et al., 2010), where it colocalizes with the cadherin–catenin complex.”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Sun et al., 2009
Scribble knockdown alters synaptic vesicle clustering, although synapse number and localization of key synaptic proteins remain unchanged.
“As in Drosophila, Scribble knockdown alters synaptic vesicle clustering, although synapse number and localization of key synaptic proteins remain unchanged.”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Sun et al., 2009
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References 42 · Cited by 93
- Authors
- Sun, Y., Aiga, M., Yoshida, E., Humbert, P. O., & Bamji, S. X.
- Affiliations
- University of British Columbia (CA)
- Peter MacCallum Cancer Centre (AU)
- Venue
- Molecular Biology of the Cell
- Published
- 2009-07-15
- Volume
- 20
- Issue
- 14
- Pages
- 3390-3400
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2710836
- OpenAlex
- W2142899990
- Cited by
- 93
- References
- 42
- Citations by year
- 2023: 2 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 8 · 2013: 8 · 2012: 9
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- Cancer Research UK
- Canadian Institutes of Health Research
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Scribble, β-catenin, synaptic vesicle clustering, synaptic vesicle recycling, bassoon, synaptic development, protein-protein interaction, primary neurons
- MeSH terms
- Animals, Axons, Cells, Cultured, Endocytosis, Hippocampus, Protein Binding, Synaptic Vesicles, Protein Transport, RNA Interference, Intracellular Signaling Peptides and Proteins, beta Catenin, Mice, Gene Knockdown Techniques
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