CoChat
Sign Up
Cited by 119

The DOI matches its Crossref record.

LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate

Belluzzi, Elisa, Gonnelli, Adriano, Cirnaru, Maria-Daniela, Marte, Antonella, Plotegher, Nicoletta, Russo, Isabella, Civiero, Laura, Cogo, Susanna, Carrion, Maria Perèz, Franchin, Cinzia, Arrigoni, Giorgio, Beltramini, Mariano, Bubacco, Luigi, Onofri, Franco, Piccoli, Giovanni, Greggio, Elisa·2016·Molecular Neurodegeneration
DOI 10.1186/s13024-015-0066-zPMC PMC4711005
Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s13024-015-0066-z

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • LRRK2 activity plays a role in synaptic vesicle endocytosis, activation of autophagy, and axonal transport of growth factor receptors.

    “LRRK2 activity plays a role in synaptic vesicle endocytosis, activation of autophagy, and axonal transport of growth factor receptors [2, 7, 10, 24, 25, 36, 51, 59, 62, 75, 77, 96].”

    From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [7]

    The Background and Discussion link LRRK2 kinase activity to synaptic-vesicle exo/endocytosis, and the Results describe effects on vesicle recycling. Our copy does not support the other attributed roles—activation of autophagy or axonal transport of growth factor receptors (searched both phrases). (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 50

  1. Gasper R, Meyer S, Gotthardt K, Sirajuddin M, Wittinghofer A. It takes two to tango: regulation of G proteins by dimerization. Nat Rev Mol Cell Biol. 2009;10(6):423–9. doi: 10.1038/nrm2689 . · DOI
  2. Taymans JM. The GTPase function of LRRK2. Biochem Soc Trans. 2012;40(5):1063–9. doi: 10.1042/BST20120133 . · DOI
  3. Greggio E. Role of LRRK2 kinase activity in the pathogenesis of Parkinson’s disease. Biochem Soc Trans. 2012;40(5):1058–62. doi: 10.1042/BST20120054 . · DOI
  4. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44(4):595–600. doi: 10.1016/j.neuron.2004.10.023 . · DOI
  5. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004;44(4):601–7. doi: 10.1016/j.neuron.2004.11.005 . · DOI
  6. Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet. 2009;41(12):1303–7. doi: 10.1038/ng.485 . · DOI
  7. Simon-Sanchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet. 2009;41(12):1308–12. doi: 10.1038/ng.487 . · DOI · Paper page
  8. Rudenko IN, Cookson MR. Heterogeneity of leucine-rich repeat kinase 2 mutations: genetics, mechanisms and therapeutic implications. Neurotherapeutics. 2014;11(4):738–50. doi: 10.1007/s13311-014-0284-z . · DOI
  9. Reynolds A, Doggett EA, Riddle SM, Lebakken CS, Nichols RJ. LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status. Front Mol Neurosci. 2014;7:54. doi: 10.3389/fnmol.2014.00054 . · DOI
  10. Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O, et al. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet. 2009;18(21):4022–34. doi: 10.1093/hmg/ddp346 . · DOI
  11. Beilina A, Rudenko IN, Kaganovich A, Civiero L, Chau H, Kalia SK, et al. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc Natl Acad Sci. 2014;111(7):2626–31. doi: 10.1073/pnas.1318306111 . · DOI · Paper page
  12. Berger Z, Smith KA, Lavoie MJ. Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation. Biochemistry. 2010;49(26):5511–23. doi: 10.1021/bi100157u . · DOI
  13. Biskup S, Moore DJ, Celsi F, Higashi S, West AB, Andrabi SA, et al. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann Neurol. 2006;60(5):557–69. doi: 10.1002/ana.21019 . · DOI
  14. Hatano T, S-i K, Imai S, Maeda M, Ishikawa K, Mizuno Y, et al. Leucine-rich repeat kinase 2 associates with lipid rafts. Hum Mol Genet. 2007;16(6):678–90. doi: 10.1093/hmg/ddm013 . · DOI
  15. Shin N, Jeong H, Kwon J, Heo HY, Kwon JJ, Yun HJ, et al. LRRK2 regulates synaptic vesicle endocytosis. Exp Cell Res. 2008;314(10):2055–65. doi: 10.1016/j.yexcr.2008.02.015 . · DOI
  16. Beccano-Kelly DA, Kuhlmann N, Tatarnikov I, Volta M, Munsie LN, Chou P, et al. Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice. Front Cell Neurosci. 2014;8:301. doi: 10.3389/fncel.2014.00301 . · DOI · Paper page
  17. Li X, Patel JC, Wang J, Avshalumov MV, Nicholson C, Buxbaum JD, et al. Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson’s disease mutation G2019S. J Neurosci. 2010;30(5):1788–97. doi: 10.1523/JNEUROSCI.5604-09.2010 . · DOI
  18. Li Y, Liu W, Oo TF, Wang L, Tang Y, Jackson-Lewis V, et al. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson’s disease. Nat Neurosci. 2009;12(7):826–8. doi: 10.1038/nn.2349 . · DOI
  19. Tong Y, Pisani A, Martella G, Karouani M, Yamaguchi H, Pothos EN, et al. R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc Natl Acad Sci U S A. 2009;106(34):14622–7. doi: 10.1073/pnas.0906334106 . · DOI
  20. Piccoli G, Condliffe SB, Bauer M, Giesert F, Boldt K, De Astis S, et al. LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. J Neurosci. 2011;31(6):2225–37. doi: 10.1523/JNEUROSCI.3730-10.2011 . · DOI
  21. Piccoli G, Onofri F, Cirnaru MD, Kaiser CJ, Jagtap P, Kastenmuller A, et al. LRRK2 binds to neuronal vesicles through protein interactions mediated by its C-terminal WD40 domain. Mol Cell Biol. 2014;34:2147–61. doi: 10.1128/MCB.00914-13 . · DOI · Paper page
  22. Cirnaru MD, Marte A, Belluzzi E, Russo I, Gabrielli M, Longo F, et al. LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex. Front Mol Neurosci. 2014;7:49. doi: 10.3389/fnmol.2014.00049 . · DOI · Paper page
  23. Sudhof TC, Rizo J (2011) Synaptic vesicle exocytosis. Cold Spring Harb Perspect Biol 3 (12). doi: 10.1101/cshperspect.a005637 · DOI
  24. Huynh H, Bottini N, Williams S, Cherepanov V, Musumeci L, Saito K, et al. Control of vesicle fusion by a tyrosine phosphatase. Nat Cell Biol. 2004;6(9):831–9. doi: 10.1038/ncb1164 . · DOI
  25. Liu Y, Cheng K, Gong K, Fu AK, Ip NY. Pctaire1 phosphorylates N-ethylmaleimide-sensitive fusion protein: implications in the regulation of its hexamerization and exocytosis. J Biol Chem. 2006;281(15):9852–8. doi: 10.1074/jbc.M513496200 . · DOI
  26. Matveeva EA, Whiteheart SW, Vanaman TC, Slevin JT. Phosphorylation of the N-ethylmaleimide-sensitive factor is associated with depolarization-dependent neurotransmitter release from synaptosomes. J Biol Chem. 2001;276(15):12174–81. doi: 10.1074/jbc.M007394200 . · DOI
  27. Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, et al. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012;22(17):5625–9. doi: 10.1016/j.bmcl.2012.06.104 . · DOI
  28. Melrose HL, Dachsel JC, Behrouz B, Lincoln SJ, Yue M, Hinkle KM, et al. Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice. Neurobiol Dis. 2010;40(3):503–17. doi: 10.1016/j.nbd.2010.07.010 . · DOI
  29. Granseth B, Odermatt B, Royle SJ, Lagnado L. Clathrin-mediated endocytosis is the dominant mechanism of vesicle retrieval at hippocampal synapses. Neuron. 2006;51(6):773–86. doi: 10.1016/j.neuron.2006.08.029 . · DOI
  30. Matteoli M, Takei K, Perin MS, Sudhof TC, De Camilli P. Exo-endocytotic recycling of synaptic vesicles in developing processes of cultured hippocampal neurons. J Cell Biol. 1992;117(4):849–61. · DOI
  31. Civiero L, Vancraenenbroeck R, Belluzzi E, Beilina A, Lobbestael E, Reyniers L, et al. Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers. PLoS One. 2012;7(8):e43472. doi: 10.1371/journal.pone.0043472 . · DOI
  32. Webber PJ, Smith AD, Sen S, Renfrow MB, Mobley JA, West AB. Autophosphorylation in the leucine-rich repeat kinase 2 (LRRK2) GTPase domain modifies kinase and GTP-binding activities. J Mol Biol. 2011;412(1):94–110. doi: 10.1016/j.jmb.2011.07.033 . · DOI
  33. Zhao C, Slevin JT, Whiteheart SW. Cellular functions of NSF: not just SNAPs and SNAREs. FEBS Lett. 2007;581(11):2140–9. doi: 10.1016/j.febslet.2007.03.032 . · DOI
  34. Cipriano DJ, Jung J, Vivona S, Fenn TD, Brunger AT, Bryant Z. Processive ATP-driven Substrate Disassembly by the N-Ethylmaleimide-sensitive Factor (NSF) Molecular Machine. J Biol Chem. 2013;288(32):23436–45. doi: 10.1074/jbc.M113.476705 . · DOI
  35. Vivona S, Cipriano DJ, O’Leary S, Li YH, Fenn TD, Brunger AT. Disassembly of all SNARE complexes by N-ethylmaleimide-sensitive factor (NSF) is initiated by a conserved 1:1 interaction between alpha-soluble NSF attachment protein (SNAP) and SNARE complex. J Biol Chem. 2013;288(34):24984–91. doi: 10.1074/jbc.M113.489807 . · DOI
  36. Yun HJ, Park J, Ho DH, Kim H, Kim C-H, Oh H, et al. LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25. Exp Mol Med. 2013;45:e36. doi: 10.1038/emm.2013.68 . · DOI
  37. Arranz AM, Delbroek L, Van Kolen K, Guimaraes MR, Mandemakers W, Daneels G, et al. LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism. J Cell Sci. 2015;128(3):541–52. doi: 10.1242/jcs.158196 . · DOI · Paper page
  38. Matta S, Van Kolen K, da Cunha R, van den Bogaart G, Mandemakers W, Miskiewicz K, et al. LRRK2 Controls an EndoA Phosphorylation Cycle in Synaptic Endocytosis. Neuron. 2012;75(6):1008–21. http://dx.doi.org/10.1016/j.neuron.2012.08.022 . · DOI · Paper page
  39. Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, et al. Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson’s disease. Cell. 2014;157(2):472–85. doi: 10.1016/j.cell.2014.01.064 . · DOI · Paper page
  40. Matveeva EA, He P, Whiteheart SW. N-Ethylmaleimide-sensitive fusion protein contains high and low affinity ATP-binding sites that are functionally distinct. J Biol Chem. 1997;272(42):26413–8. · DOI
  41. Yu RC, Hanson PI, Jahn R, Brunger AT. Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP. Nat Struct Biol. 1998;5(9):803–11. doi: 10.1038/1843 . · DOI
  42. Liu G, Sgobio C, Gu X, Sun L, Lin X, Yu J, Parisiadou L, Xie C, Sastry N, Ding J, Lohr KM, Miller GW, Mateo Y, Lovinger DM, Cai H (2015) Selective Expression of Parkinson’s disease-related Leucine-rich Repeat Kinase 2 G2019S Missense Mutation in Midbrain Dopaminergic Neurons Impairs Dopamine Release and Dopaminergic Gene Expression. Hum Mol Genet. doi: 10.1093/hmg/ddv249 · DOI
  43. Fuji RN, Flagella M, Baca M, Baptista MA, Brodbeck J, Chan BK, et al. Effect of selective LRRK2 kinase inhibition on nonhuman primate lung. Sci Transl Med. 2015;7(273):273ra215. doi: 10.1126/scitranslmed.aaa3634 . · DOI
  44. Piccoli G, Verpelli C, Tonna N, Romorini S, Alessio M, Nairn AC, et al. Proteomic analysis of activity-dependent synaptic plasticity in hippocampal neurons. J Proteome Res. 2007;6(8):3203–15. doi: 10.1021/pr0701308 . · DOI
  45. Nakamura Y, Iga K, Shibata T, Shudo M, Kataoka K. Glial plasmalemmal vesicles: a subcellular fraction from rat hippocampal homogenate distinct from synaptosomes. Glia. 1993;9(1):48–56. doi: 10.1002/glia.440090107 . · DOI
  46. Sankaranarayanan S, Ryan TA. Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system. Nat Cell Biol. 2000;2(4):197–204. doi: 10.1038/35008615 . · DOI
  47. Verderio C, Coco S, Bacci A, Rossetto O, De Camilli P, Montecucco C, et al. Tetanus toxin blocks the exocytosis of synaptic vesicles clustered at synapses but not of synaptic vesicles in isolated axons. J Neurosci. 1999;19(16):6723–32. · DOI
  48. Salvi M, Trashi E, Cozza G, Franchin C, Arrigoni G, Pinna LA. Investigation on PLK2 and PLK3 substrate recognition. Biochim Biophys Acta. 2012;1824(12):1366–73. doi: 10.1016/j.bbapap.2012.07.003 . · DOI
  49. Venerando A, Franchin C, Cant N, Cozza G, Pagano MA, Tosoni K, et al. Detection of phospho-sites generated by protein kinase CK2 in CFTR: mechanistic aspects of Thr1471 phosphorylation. PLoS One. 2013;8(9):e74232. doi: 10.1371/journal.pone.0074232 . · DOI
  50. Lanzetta PA, Alvarez LJ, Reinach PS, Candia OA. An improved assay for nanomole amounts of inorganic phosphate. Anal Biochem. 1979;100(1):95–7. · DOI

Cited by

Sorted by citations

Metadata

Authors
Belluzzi, E., Gonnelli, A., Cirnaru, M.-D., Marte, A., Plotegher, N., Russo, I., Civiero, L., Cogo, S., Carrion, M. P., Franchin, C., Arrigoni, G., Beltramini, M., Bubacco, L., Onofri, F., Piccoli, G., & Greggio, E.
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2016-01-13
Volume
11
Issue
1
ISSN
1750-1326
DOI
10.1186/s13024-015-0066-z
PMC
PMC4711005
Cited by
119
References
0
Language
en
Funders
  • Michael J. Fox Foundation for Parkinson's Research (US)
  • Fondazione Telethon (IT) (GGP12237)
  • Progetto di Ateneo CPDA University pf Padova (124045/12)
  • Regione Lombardia (18099/RCC)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review