ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 76 citations in OpenAlex.
- Structural Determinants of Synaptic Vesicle Protein 2C Ligand Selectivity and Their Impact on Dopamine Release.bioRxiv : the preprint server for biology · 2026Article
- Selective Brain-Penetrant TTBK1 Inhibitors Modulate TDP-43 Pathology and Rescue Cognitive Deficits in a Mouse Model of TDP-43 Proteinopathy.Journal of medicinal chemistry · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Missense variant in TTBK2 kinase domain causes loss of function and impaired protein phosphorylation.Scientific reports · 2025Article
- Structures of native SV2A reveal the binding mode for tetanus neurotoxin and anti-epileptic racetams.Nature communications · 2025Article
- Control of Synaptotagmin-1 Trafficking by SV2A-Mechanism and Consequences for Presynaptic Function and Dysfunction.Journal of neurochemistry · 2025Review
- Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.Nature structural & molecular biology · 2024Article
- Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Review
- Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil.Neuroscience bulletin · 2024Review
- Spinocerebellar ataxia type 11 (SCA11): TTBK2 variants, functions and associated disease mechanisms.Cerebellum (London, England) · 2024Review
- Increased presynaptic excitability in a migraine with aura mutation.Brain : a journal of neurology · 2024Article
- Synaptotagmin-11 Inhibits Synaptic Vesicle Endocytosis via Endophilin A1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Presynaptic targeting of botulinum neurotoxin type A requires a tripartite PSG-Syt1-SV2 plasma membrane nanocluster for synaptic vesicle entry.The EMBO journal · 2023Article
- N-glycoproteomics of brain synapses and synaptic vesicles.Cell reports · 2023Article
- Exploiting the molecular diversity of the synapse to investigate neuronal communication: A guide through the current toolkit.The European journal of neuroscience · 2022Review
- Brivaracetam and Levetiracetam Suppress Astroglial L-Glutamate Release through Hemichannel via Inhibition of Synaptic Vesicle Protein.International journal of molecular sciences · 2022Article
- FMRP Sustains Presynaptic Function via Control of Activity-Dependent Bulk Endocytosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- All-optical monitoring of excitation-secretion coupling demonstrates that SV2A functions downstream of evoked CaThe Journal of physiology · 2022Article
- CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders.Frontiers in molecular biosciences · 2022Review
- Synaptic Secretion and Beyond: Targeting Synapse and Neurotransmitters to Treat Neurodegenerative Diseases.Oxidative medicine and cellular longevity · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Synaptic vesicle protein 2A (SV2A) is a ubiquitous component of synaptic vesicles (SVs). It has roles in both SV trafficking and neurotransmitter release. We demonstrate that Casein kinase 1 family members, including isoforms of Tau-tubulin protein kinases (TTBK1 and TTBK2), phosphorylate human SV2A at two constellations of residues, namely Cluster-1 (Ser42, Ser45, and Ser47) and Cluster-2 (Ser80, Ser81, and Thr84). These residues are also phosphorylated in vivo, and the phosphorylation of Thr84 within Cluster-2 is essential for triggering binding to the C2B domain of human synaptotagmin-1. We show by crystallographic and other analyses that the phosphorylated Thr84 residue binds to a pocket formed by three conserved Lys residues (Lys314, Lys326, and Lys328) on the surface of the synaptotagmin-1 C2B domain. Finally, we observed dysfunctional synaptotagmin-1 retrieval during SV endocytosis by ablating its phospho-dependent interaction with SV2A, knockdown of SV2A, or rescue with a phosphorylation-null Thr84 SV2A mutant in primary cultures of mouse neurons. This study reveals fundamental details of how phosphorylation of Thr84 on SV2A controls its interaction with synaptotagmin-1 and implicates SV2A as a phospho-dependent chaperone required for the specific retrieval of synaptotagmin-1 during SV endocytosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.