4v11 › Citations

Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1.

Zhang N, Gordon SL, Fritsch MJ, Esoof N, Campbell DG, Gourlay R, Velupillai S, Macartney T, Peggie M, van Aalten DM, Cousin MA, Alessi DR
J Neurosci 35 2492-507 (2015)
Cited: 44 times
EuropePMC logo PMID: 25673844

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.

Articles - 4v11 mentioned but not cited (3)

  1. Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1. Zhang N, Gordon SL, Fritsch MJ, Esoof N, Campbell DG, Gourlay R, Velupillai S, Macartney T, Peggie M, van Aalten DM, Cousin MA, Alessi DR. J Neurosci 35 2492-2507 (2015)
  2. In Silico and In Vivo: Evaluating the Therapeutic Potential of Kaempferol, Quercetin, and Catechin to Treat Chronic Epilepsy in a Rat Model. Ahmed H, Khan MA, Ali Zaidi SA, Muhammad S. Front Bioeng Biotechnol 9 754952 (2021)
  3. Functional Characterization of the N-Terminal C2 Domain from Arabidopsis thaliana Phospholipase Dα and Dβ. Rahier R, Noiriel A, Abousalham A. Biomed Res Int 2016 2721719 (2016)


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  1. Microtubule plus-end tracking proteins in neuronal development. van de Willige D, Hoogenraad CC, Akhmanova A. Cell Mol Life Sci 73 2053-2077 (2016)
  2. Puzzling Out Synaptic Vesicle 2 Family Members Functions. Bartholome O, Van den Ackerveken P, Sánchez Gil J, de la Brassinne Bonardeaux O, Leprince P, Franzen R, Rogister B. Front Mol Neurosci 10 148 (2017)
  3. Structure, regulation, and (patho-)physiological functions of the stress-induced protein kinase CK1 delta (CSNK1D). Xu P, Ianes C, Gärtner F, Liu C, Burster T, Bakulev V, Rachidi N, Knippschild U, Bischof J. Gene 715 144005 (2019)
  4. Integration of Synaptic Vesicle Cargo Retrieval with Endocytosis at Central Nerve Terminals. Cousin MA. Front Cell Neurosci 11 234 (2017)
  5. The iTRAPs: Guardians of Synaptic Vesicle Cargo Retrieval During Endocytosis. Gordon SL, Cousin MA. Front Synaptic Neurosci 8 1 (2016)
  6. Synaptic vesicle protein 2: A multi-faceted regulator of secretion. Ciruelas K, Marcotulli D, Bajjalieh SM. Semin Cell Dev Biol 95 130-141 (2019)
  7. Tau tubulin kinases in proteinopathy. Taylor LM, McMillan PJ, Kraemer BC, Liachko NF. FEBS J 286 2434-2446 (2019)
  8. Molecular Signatures Underlying Synaptic Vesicle Cargo Retrieval. Mori Y, Takamori S. Front Cell Neurosci 11 422 (2017)
  9. Safeguards of Neurotransmission: Endocytic Adaptors as Regulators of Synaptic Vesicle Composition and Function. Kaempf N, Maritzen T. Front Cell Neurosci 11 320 (2017)
  10. Synaptic Vesicle Glycoprotein 2A: Features and Functions. Rossi R, Arjmand S, Bærentzen SL, Gjedde A, Landau AM. Front Neurosci 16 864514 (2022)
  11. Synaptic Secretion and Beyond: Targeting Synapse and Neurotransmitters to Treat Neurodegenerative Diseases. Wei Z, Wei M, Yang X, Xu Y, Gao S, Ren K. Oxid Med Cell Longev 2022 9176923 (2022)
  12. Exploiting the molecular diversity of the synapse to investigate neuronal communication: A guide through the current toolkit. Lamanna J, Ferro M, Spadini S, Malgaroli A. Eur J Neurosci 56 6141-6161 (2022)
  13. CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders. Baier A, Szyszka R. Front Mol Biosci 9 916063 (2022)
  14. Positron Emission Computed Tomography Imaging of Synaptic Vesicle Glycoprotein 2A in Alzheimer's Disease. Kong Y, Zhang S, Huang L, Zhang C, Xie F, Zhang Z, Huang Q, Jiang D, Li J, Zhou W, Hua T, Sun B, Wang J, Guan Y. Front Aging Neurosci 13 731114 (2021)
  15. Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil. Wu PP, Cao BR, Tian FY, Gao ZB. Neurosci Bull (2023)
  16. Spinocerebellar ataxia type 11 (SCA11): TTBK2 variants, functions and associated disease mechanisms. Felício D, Santos M. Cerebellum (2023)

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  1. A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. Clairfeuille T, Mas C, Chan AS, Yang Z, Tello-Lafoz M, Chandra M, Widagdo J, Kerr MC, Paul B, Mérida I, Teasdale RD, Pavlos NJ, Anggono V, Collins BM. Nat Struct Mol Biol 23 921-932 (2016)
  2. Activity-Dependent Degradation of Synaptic Vesicle Proteins Requires Rab35 and the ESCRT Pathway. Sheehan P, Zhu M, Beskow A, Vollmer C, Waites CL. J Neurosci 36 8668-8686 (2016)
  3. VAMP4 Is an Essential Cargo Molecule for Activity-Dependent Bulk Endocytosis. Nicholson-Fish JC, Kokotos AC, Gillingwater TH, Smillie KJ, Cousin MA. Neuron 88 973-984 (2015)
  4. Mitochondrial Calcium Uptake Modulates Synaptic Vesicle Endocytosis in Central Nerve Terminals. Marland JR, Hasel P, Bonnycastle K, Cousin MA. J Biol Chem 291 2080-2086 (2016)
  5. Brivaracetam augments short-term depression and slows vesicle recycling. Yang X, Bognar J, He T, Mohammed M, Niespodziany I, Wolff C, Esguerra M, Rothman SM, Dubinsky JM. Epilepsia 56 1899-1909 (2015)
  6. TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons. Bowie E, Goetz SC. Elife 9 e51166 (2020)
  7. A Fine Balance of Synaptophysin Levels Underlies Efficient Retrieval of Synaptobrevin II to Synaptic Vesicles. Gordon SL, Harper CB, Smillie KJ, Cousin MA. PLoS One 11 e0149457 (2016)
  8. Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles. Harper CB, Papadopulos A, Martin S, Matthews DR, Morgan GP, Nguyen TH, Wang T, Nair D, Choquet D, Meunier FA. Sci Rep 6 19654 (2016)
  9. Spinocerebellar ataxia type 11-associated alleles of Ttbk2 dominantly interfere with ciliogenesis and cilium stability. Bowie E, Norris R, Anderson KV, Goetz SC. PLoS Genet 14 e1007844 (2018)
  10. Synaptophysin sustains presynaptic performance by preserving vesicular synaptobrevin-II levels. Kokotos AC, Harper CB, Marland JRK, Smillie KJ, Cousin MA, Gordon SL. J Neurochem 151 28-37 (2019)
  11. An Epilepsy-Associated SV2A Mutation Disrupts Synaptotagmin-1 Expression and Activity-Dependent Trafficking. Harper CB, Small C, Davenport EC, Low DW, Smillie KJ, Martínez-Mármol R, Meunier FA, Cousin MA. J Neurosci 40 4586-4595 (2020)
  12. Acute inhibition of the CNS-specific kinase TTBK1 significantly lowers tau phosphorylation at several disease relevant sites. Dillon GM, Henderson JL, Bao C, Joyce JA, Calhoun M, Amaral B, King KW, Bajrami B, Rabah D. PLoS One 15 e0228771 (2020)
  13. Altered synaptobrevin-II trafficking in neurons expressing a synaptophysin mutation associated with a severe neurodevelopmental disorder. Harper CB, Mancini GMS, van Slegtenhorst M, Cousin MA. Neurobiol Dis 108 298-306 (2017)
  14. Mechanisms of Regulation and Diverse Activities of Tau-Tubulin Kinase (TTBK) Isoforms. Bao C, Bajrami B, Marcotte DJ, Chodaparambil JV, Kerns HM, Henderson J, Wei R, Gao B, Dillon GM. Cell Mol Neurobiol 41 669-685 (2021)
  15. The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer's Disease: Implications for Treatment. Kong Y, Huang L, Li W, Liu X, Zhou Y, Liu C, Zhang S, Xie F, Zhang Z, Jiang D, Zhou W, Ni R, Zhang C, Sun B, Wang J, Guan Y. Front Cell Dev Biol 9 609908 (2021)
  16. Brivaracetam and Levetiracetam Suppress Astroglial L-Glutamate Release through Hemichannel via Inhibition of Synaptic Vesicle Protein. Fukuyama K, Okada M. Int J Mol Sci 23 4473 (2022)
  17. FMRP Sustains Presynaptic Function via Control of Activity-Dependent Bulk Endocytosis. Bonnycastle K, Kind PC, Cousin MA. J Neurosci 42 1618-1628 (2022)
  18. All-optical monitoring of excitation-secretion coupling demonstrates that SV2A functions downstream of evoked Ca2+ entry. Bradberry MM, Chapman ER. J Physiol 600 645-654 (2022)
  19. Synaptophysin controls synaptobrevin-II retrieval via a cryptic C-terminal interaction site. Harper CB, Blumrich EM, Cousin MA. J Biol Chem 296 100266 (2021)
  20. Presynaptic targeting of botulinum neurotoxin type A requires a tripartite PSG-Syt1-SV2 plasma membrane nanocluster for synaptic vesicle entry. Joensuu M, Syed P, Saber SH, Lanoue V, Wallis TP, Rae J, Blum A, Gormal RS, Small C, Sanders S, Jiang A, Mahrhold S, Krez N, Cousin MA, Cooper-White R, Cooper-White JJ, Collins BM, Parton RG, Balistreri G, Rummel A, Meunier FA. EMBO J 42 e112095 (2023)
  21. Synaptic Vesicle Recycling Is Unaffected in the Ts65Dn Mouse Model of Down Syndrome. Marland JR, Smillie KJ, Cousin MA. PLoS One 11 e0147974 (2016)
  22. [Function of synaptic vesicle protein 2A (SV2A) as a novel therapeutic target for epilepsy]. Tokudome K, Shimizu S, Serikawa T, Ohno Y. Nihon Yakurigaku Zasshi 152 275-280 (2018)
  23. N-glycoproteomics of brain synapses and synaptic vesicles. Bradberry MM, Peters-Clarke TM, Shishkova E, Chapman ER, Coon JJ. Cell Rep 42 112368 (2023)
  24. Lost in Space: How a Single, Directionless Protein Can Cause So Much Mayhem. Salvati KA, Beenhakker MP. Epilepsy Curr 20 381-383 (2020)
  25. Synaptotagmin-11 Inhibits Synaptic Vesicle Endocytosis via Endophilin A1. Wang Y, Zhu Y, Li W, Yan S, Li C, Ma K, Hu M, Du C, Fu L, Sun J, Zhang CX. J Neurosci 43 6230-6248 (2023)


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