The Sybtraps: Control of Synaptobrevin Traffic by Synaptophysin, α-Synuclein and AP-180

Synaptobrevin II (sybII) is a key fusogenic molecule on synaptic vesicles (SVs) therefore the active maintenance of both its conformation and location in sufficient numbers on this organelle is critical in both mediating and sustaining neurotransmitter release. Recently three proteins have been identified having key roles in the presentation, trafficking and retrieval of sybII during the fusion and endocytosis of SVs. The nerve terminal protein α‐synuclein catalyses sybII entry into SNARE complexes, whereas the monomeric adaptor protein AP‐180 is required for sybII retrieval during SV endocytosis. Overarching these events is the tetraspan SV protein synaptophysin, which is a major sybII interaction partner on the SV. This review will evaluate recent studies to propose working models for the control of sybII traffic by synaptophysin and other Sybtraps (sybII trafficking partners) and suggest how dysfunction in sybII traffic may contribute to human disease.

• Publication year

  2013

• Venue

  Traffic : the International Journal of Intracellular Transport

• Publication date

  2013-12-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/tra.12140PMID 24279465PMCID 3992847
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

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• The function of α-synuclein.

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• X-Linked Intellectual Disability-Associated Mutations in Synaptophysin Disrupt Synaptobrevin II Retrieval

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• Deleterious effects of soluble amyloid-β oligomers on multiple steps of synaptic vesicle trafficking.

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• SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses

  2011influential reference
• v-SNARE composition distinguishes synaptic vesicle pools.

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• Protein Quantification at the Single Vesicle Level Reveals That a Subset of Synaptic Vesicle Proteins Are Trafficked with High Precision

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• Synaptophysin Is Required for Synaptobrevin Retrieval during Synaptic Vesicle Endocytosis

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• Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons.

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• Calcium dependence of exo- and endocytotic coupling at a glutamatergic synapse.

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• Structure of synaptophysin: a hexameric MARVEL-domain channel protein.

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• Synaptophysin I selectively specifies the exocytic pathway of synaptobrevin 2/VAMP2.

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• Determinants of synaptobrevin regulation in membranes.

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• Beta-amyloid disrupted synaptic vesicle endocytosis in cultured hippocampal neurons.

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• The Synaptophysin–Synaptobrevin Complex: a Hallmark of Synaptic Vesicle Maturation

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