ArticleThe Journal of cell biology2001
The AP2 binding site of synaptotagmin 1 is not an internalization signal but a regulator of endocytosis.
Article in The Journal of cell biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 54 citations in OpenAlex.
- Synaptotagmin-1 is a bidirectional CaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Function of Drosophila Synaptotagmins in membrane trafficking at synapses.Cellular and molecular life sciences : CMLS · 2021Review
- Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations.Cells · 2019Review
- Synaptotagmin 2 Is the Fast CaCell reports · 2017Article
- Safeguards of Neurotransmission: Endocytic Adaptors as Regulators of Synaptic Vesicle Composition and Function.Frontiers in cellular neuroscience · 2017Review
- Molecular Mechanisms for the Coupling of Endocytosis to Exocytosis in Neurons.Frontiers in molecular neuroscience · 2017Review
- Synaptotagmin-11 inhibits clathrin-mediated and bulk endocytosis.EMBO reports · 2016Article
- Presynaptic membrane retrieval and endosome biology: defining molecularly heterogeneous synaptic vesicles.Cold Spring Harbor perspectives in biology · 2013Review
- Endocytosis and intracellular trafficking contribute to necrotic neurodegeneration in C. elegans.The EMBO journal · 2012Article
- Post-translational modifications and lipid binding profile of insect cell-expressed full-length mammalian synaptotagmin 1.Biochemistry · 2011Article
- RNAi screen identifies a role for adaptor protein AP-3 in sorting to the regulated secretory pathway.The Journal of cell biology · 2010Article
- Molecular basis of synaptic vesicle cargo recognition by the endocytic sorting adaptor stonin 2.The Journal of cell biology · 2007Article
- Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII.Biochemical and biophysical research communications · 2007Article
- Synaptophysin I selectively specifies the exocytic pathway of synaptobrevin 2/VAMP2.The Biochemical journal · 2007Article
- C2B polylysine motif of synaptotagmin facilitates a Ca2+-independent stage of synaptic vesicle priming in vivo.Molecular biology of the cell · 2006Article
- Article
- Effects of synaptotagmin reveal two distinct mechanisms of agonist-stimulated internalization of the M4 muscarinic acetylcholine receptor.British journal of pharmacology · 2005Article
- Synaptotagmin 7 splice variants differentially regulate synaptic vesicle recycling.The EMBO journal · 2003Article
- Role of synaptotagmin in Ca2+-triggered exocytosis.The Biochemical journal · 2002Review
- The abscisic acid-related SNARE homolog NtSyr1 contributes to secretion and growth: evidence from competition with its cytosolic domain.The Plant cell · 2002Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
One characteristic linking members of the synaptotagmin family to endocytosis is their ability to bind the heterotetrameric AP2 complex via their C2B domain. By using CD4/synaptotagmin 1 chimeras, we found that the internalization signal of synaptotagmin 1 lies at the extreme COOH-terminus of the protein and can function in the absence of the C2B domain that contains the AP2 binding site. However, although not essential for internalization, the C2B domain of synaptotagmin 1 appeared to control the recognition of the internalization motif. By mutagenesis, two sites have been identified that modify regulation by the C2B domain in the neuroendocrine PC12 cell line. Mutation of a dilysine motif in the beta sandwich core of the domain eliminates endocytosis. This site is known to be a site of protein-protein interaction. Mutations in the calcium binding region, or in its close proximity, also affect internalization in PC12 cells. In fibroblasts, the C2B domain inhibits the COOH-terminal internalization signal, resulting in an absence of internalization in those cells. Thus, internalization of synaptotagmin 1 is controlled by the presence of a latent internalization signal in the COOH-terminal region and a regulatory region in the C2B domain. We propose that internalization of synaptotagmin 1 is regulated in this way to allow it to couple the processes of endocytosis and calcium-mediated exocytosis in cells of the neuroendocrine lineage.
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