CoChat
Sign Up
Cited by 22Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsGenetics and Neurodevelopmental Disorders

Ultrastructural abnormalities in CA1 hippocampus caused by deletion of the actin regulator WAVE-1

Open access
Hazai, Diána, Szudoczki, Róbert, Ding, Jindong, Soderling, Scott H., Weinberg, Richard J., Sótonyi, Péter, Rácz, Bence·2013·PLoS ONE
DOI 10.1371/journal.pone.0075248PMC PMC3783472
Open this paper in CoChat — free accountOpen PDF

Abstract

By conveying signals from the small GTPase family of proteins to the Arp2/3 complex, proteins of the WAVE family facilitate actin remodeling. The WAVE-1 isoform is expressed at high levels in brain, where it plays a role in normal synaptic processing, and is implicated in hippocampus-dependent memory retention. We used electron microscopy to determine whether synaptic structure is modified in the hippocampus of WAVE-1 knockout mice, focusing on the neuropil of CA1 stratum radiatum. Mice lacking WAVE-1 exhibited alterations in the morphology of both axon terminals and dendritic spines; the relationship between the synaptic partners was also modified. The abnormal synaptic morphology we observed suggests that signaling through WAVE-1 plays a critical role in establishing normal synaptic architecture in the rodent hippocampus.

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 · 10.1371/journal.pone.0075248

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

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

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

Cites

Flagged first, then by citations

Research works printed but not linked: 48

  1. [1]Fortin DA, Srivastava T, Soderling TR (2012) Structural modulation of dendritic spines during synaptic plasticity. Neuroscientist 18: 326- 341. doi: 10.1177/1073858411407206. PubMed: 21670426. 21670426 · DOI
  2. [2]Lippman J, Dunaevsky A (2005) Dendritic spine morphogenesis and plasticity. J Neurobiol 64: 47- 57. doi: 10.1002/neu.20149. PubMed: 15884005. 15884005 · DOI · Paper page
  3. [3]Nakagawa T, Engler JA, Sheng M (2004) The dynamic turnover and functional roles of alpha-actinin in dendritic spines. Neuropharmacology 47: 734- 745. doi: 10.1016/j.neuropharm.2004.07.022. PubMed: 15458845. 15458845 · DOI
  4. [4]Matus A (2000) Actin-based plasticity in dendritic spines. Science 290: 754- 758. doi: 10.1126/science.290.5492.754. PubMed: 11052932. 11052932 · DOI · Paper page
  5. [5]Fifková E, Delay RJ (1982) Cytoplasmic actin in neuronal processes as a possible mediator of synaptic plasticity. J Cell Biol 95: 345- 350. doi: 10.1083/jcb.95.1.345. PubMed: 6890558. 6890558 PMC2112353 · DOI · Paper page
  6. [6]Gotow T, Miyaguchi K, Hashimoto PH (1991) Cytoplasmic architecture of the axon terminal: filamentous strands specifically associated with synaptic vesicles. Neuroscience 40: 587- 598. doi: 10.1016/0306-4522(91)90143-C. PubMed: 2027472. 2027472 · DOI
  7. [7]Morales M, Colicos MA, Goda Y (2000) Actin-dependent regulation of neurotransmitter release at central synapses. Neuron 27: 539- 550. doi: 10.1016/S0896-6273(00)00064-7. PubMed: 11055436. 11055436 · DOI · Paper page
  8. [8]Cingolani LA, Goda Y (2008) Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy. Nat Rev Neurosci 9: 344- 356. doi: 10.1038/nrn2373. PubMed: 18425089. 18425089 · DOI · Paper page
  9. [9]Jensen V, Walaas SI, Hilfiker S, Ruiz A, Hvalby O (2007) A delayed response enhancement during hippocampal presynaptic plasticity in mice. J Physiol 583: 129- 143. doi: 10.1113/jphysiol.2007.131300. PubMed: 17569738. 17569738 PMC2277251 · DOI · Paper page
  10. [10]Murakoshi H, Yasuda R (2012) Postsynaptic signaling during plasticity of dendritic spines. Trends Neurosci 35: 135- 143. doi: 10.1016/j.tins.2011.12.002. PubMed: 22222350. 22222350 PMC3306839 · DOI · Paper page
  11. [11]Haditsch U, Leone DP, Farinelli M, Chrostek-Grashoff A, Brakebusch C et al. (2009) A central role for the small GTPase Rac1 in hippocampal plasticity and spatial learning and memory. Mol Cell Neurosci 41: 409- 419. doi: 10.1016/j.mcn.2009.04.005. PubMed: 19394428. 19394428 PMC2705331 · DOI
  12. [12]Tolias KF, Duman JG, Um K (2011) Control of synapse development and plasticity by Rho GTPase regulatory proteins. Prog Neurobiol 94: 133- 148. doi: 10.1016/j.pneurobio.2011.04.011. PubMed: 21530608. 21530608 PMC3129138 · DOI · Paper page
  13. [13]Brünig I, Kaech S, Brinkhaus H, Oertner TG, Matus A (2004) Influx of extracellular calcium regulates actin-dependent morphological plasticity in dendritic spines. Neuropharmacology 47: 669- 676. doi: 10.1016/j.neuropharm.2004.07.038. PubMed: 15458838. 15458838 · DOI
  14. [14]Sanhueza M, Fernandez-Villalobos G, Stein IS, Kasumova G, Zhang P et al. (2011) Role of the CaMKII/NMDA receptor complex in the maintenance of synaptic strength. J Neurosci 31: 9170- 9178. doi: 10.1523/JNEUROSCI.1250-11.2011. PubMed: 21697368. 21697368 PMC3138556 · DOI · Paper page
  15. [15]Ultanir SK, Kim JE, Hall BJ, Deerinck T, Ellisman M et al. (2007) Regulation of spine morphology and spine density by NMDA receptor signaling in vivo. Proc Natl Acad Sci U S A 104: 19553- 19558. doi: 10.1073/pnas.0704031104. PubMed: 18048342. 18048342 PMC2148327 · DOI · Paper page
  16. [16]Heasman SJ, Ridley AJ (2008) Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol 9: 690- 701. doi: 10.1038/nrm2476. PubMed: 18719708. 18719708 · DOI · Paper page
  17. [17]Choi J, Ko J, Racz B, Burette A, Lee JR et al. (2005) Regulation of dendritic spine morphogenesis by insulin receptor substrate 53, a downstream effector of Rac1 and Cdc42 small GTPases. J Neurosci 25: 869- 879. doi: 10.1523/JNEUROSCI.3212-04.2005. PubMed: 15673667. 15673667 PMC6725612 · DOI
  18. [18]Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420: 629- 635. doi: 10.1038/nature01148. PubMed: 12478284. 12478284 · DOI
  19. [19]Gonzalez-Billault C, Muñoz-Llancao P, Henriquez DR, Wojnacki J, Conde C et al. (2012) The role of small GTPases in neuronal morphogenesis and polarity. Cytoskeleton (Hoboken) 69: 464- 485. doi: 10.1002/cm.21034. PubMed: 22605667. 22605667 · DOI
  20. [20]Machesky LM, Insall RH (1998) Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol 8: 1347- 1356. doi: 10.1016/S0960-9822(98)00015-3. PubMed: 9889097. 9889097 · DOI
  21. [21]Soderling SH, Guire ES, Kaech S, White J, Zhang F et al. (2007) A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory. J Neurosci 27: 355- 365. doi: 10.1523/JNEUROSCI.3209-06.2006. PubMed: 17215396. 17215396 PMC3740594 · DOI · Paper page
  22. [22]Tahirovic S, Hellal F, Neukirchen D, Hindges R, Garvalov BK et al. (2010) Rac1 regulates neuronal polarization through the WAVE complex. J Neurosci 30: 6930- 6943. doi: 10.1523/JNEUROSCI.5395-09.2010. PubMed: 20484635. 20484635 PMC6632643 · DOI
  23. [23]Takenawa T, Suetsugu S (2007) The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol 8: 37- 48. doi: 10.1038/nrm2069. PubMed: 17183359. 17183359 · DOI · Paper page
  24. [24]Eden S, Rohatgi R, Podtelejnikov AV, Mann M, Kirschner MW (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418: 790- 793. doi: 10.1038/nature00859. PubMed: 12181570. 12181570 · DOI · Paper page
  25. [25]Ceglia I, Kim Y, Nairn AC, Greengard P (2010) Signaling pathways controlling the phosphorylation state of WAVE1, a regulator of actin polymerization. J Neurochem 114: 182- 190. PubMed: 20403076. 20403076 PMC2945298
  26. [26]Miki H, Takenawa T (2003) Regulation of actin dynamics by WASP family proteins. J Biochem 134: 309- 313. doi: 10.1093/jb/mvg146. PubMed: 14561714. 14561714 · DOI
  27. [27]Soderling SH, Langeberg LK, Soderling JA, Davee SM, Simerly R et al. (2003) Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice. Proc Natl Acad Sci U S A 100: 1723- 1728. doi: 10.1073/pnas.0438033100. PubMed: 12578964. 12578964 PMC149900 · DOI · Paper page
  28. [28]Soderling SH, Scott JD (2006) WAVE signalling: from biochemistry to biology. Biochem Soc Trans 34: 73- 76. doi: 10.1042/BST0340073. PubMed: 16417486. 16417486 · DOI
  29. [29]Kim Y, Sung JY, Ceglia I, Lee KW, Ahn JH et al. (2006) Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology. Nature 442: 814- 817. doi: 10.1038/nature04976. PubMed: 16862120. 16862120 · DOI · Paper page
  30. [32]Wegner AM, Nebhan CA, Hu L, Majumdar D, Meier KM et al. (2008) N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses. J Biol Chem 283: 15912- 15920. doi: 10.1074/jbc.M801555200. PubMed: 18430734. 18430734 PMC2414292 · DOI
  31. [33]Spillane M, Ketschek A, Jones SL, Korobova F, Marsick B et al. (2011) The actin nucleating Arp2/3 complex contributes to the formation of axonal filopodia and branches through the regulation of actin patch precursors to filopodia. Dev Neurobiol 71: 747- 758. doi: 10.1002/dneu.20907. PubMed: 21557512. 21557512 PMC3154400 · DOI
  32. [34]Stavoe AK, Nelson JC, Martínez-Velázquez LA, Klein M, Samuel AD et al. (2012) Synaptic vesicle clustering requires a distinct MIG-10/Lamellipodin isoform and ABI-1 downstream from Netrin. Genes Dev 26: 2206- 2221. doi: 10.1101/gad.193409.112. PubMed: 23028145. 23028145 PMC3465741 · DOI
  33. [35]Fiala JC (2005) Reconstruct: a free editor for serial section microscopy. J Microsc 218: 52- 61. doi: 10.1111/j.1365-2818.2005.01466.x. PubMed: 15817063. 15817063 · DOI
  34. [36]Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9: 671- 675. doi: 10.1038/nmeth.2089. PubMed: 22930834. 22930834 PMC5554542 · DOI · Paper page
  35. [37]Sanchez AM, Flamini MI, Genazzani AR, Simoncini T (2013) Effects of progesterone and medroxyprogesterone on actin remodeling and neuronal spine formation. Mol Endocrinol 27: 693- 702. doi: 10.1210/me.2012-1278. PubMed: 23487486. 23487486 PMC5416805 · DOI
  36. [40]Nozumi M, Nakagawa H, Miki H, Takenawa T, Miyamoto S (2003) Differential localization of WAVE isoforms in filopodia and lamellipodia of the neuronal growth cone. J Cell Sci 116: 239- 246. doi: 10.1242/jcs.00233. PubMed: 12482910. 12482910 · DOI
  37. [41]Schenck A, Qurashi A, Carrera P, Bardoni B, Diebold C et al. (2004) WAVE/SCAR, a multifunctional complex coordinating different aspects of neuronal connectivity. Dev Biol 274: 260- 270. doi: 10.1016/j.ydbio.2004.07.009. PubMed: 15385157. 15385157 · DOI · Paper page
  38. [42]Grove M, Demyanenko G, Echarri A, Zipfel PA, Quiroz ME et al. (2004) ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory. Mol Cell Biol 24: 10905- 10922. doi: 10.1128/MCB.24.24.10905-10922.2004. PubMed: 15572692. 15572692 PMC533973 · DOI · Paper page
  39. [43]Proepper C, Steinestel K, Schmeisser MJ, Heinrich J, Steinestel J et al. (2011) Heterogeneous nuclear ribonucleoprotein k interacts with Abi-1 at postsynaptic sites and modulates dendritic spine morphology. PLOS ONE 6: e27045. doi: 10.1371/journal.pone.0027045. PubMed: 22102872. 22102872 PMC3216941 · DOI
  40. [44]Kim IH, Racz B, Wang H, Burianek L, Weinberg R et al. (2013) Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities. J Neurosci 33: 6081- 6092. doi: 10.1523/JNEUROSCI.0035-13.2013. PubMed: 23554489. 23554489 PMC3656411 · DOI · Paper page
  41. [45]Marra V, Burden JJ, Thorpe JR, Smith IT, Smith SL et al. (2012) A preferentially segregated recycling vesicle pool of limited size supports neurotransmission in native central synapses. Neuron 76: 579- 589. doi: 10.1016/j.neuron.2012.08.042. PubMed: 23141069. 23141069 PMC3526798 · DOI
  42. [46]Penzes P, Rafalovich I (2012) Regulation of the actin cytoskeleton in dendritic spines. Adv Exp Med Biol 970: 81- 95. doi: 10.1007/978-3-7091-0932-8_4. PubMed: 22351052. 22351052 PMC3576144 · DOI
  43. [47]Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM (2011) Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci 14: 285- 293. doi: 10.1038/nn.2741. PubMed: 21346746. 21346746 PMC3530413 · DOI · Paper page
  44. [48]Bourne JN, Harris KM (2008) Balancing structure and function at hippocampal dendritic spines. Annu Rev Neurosci 31: 47- 67. PubMed: 18284372. 18284372 PMC2561948
  45. [49]Harris KM, Weinberg RJ (2012) Ultrastructure of synapses in the mammalian brain. Cold Spring Harb Perspect Biol. PMC3331701 22357909
  46. [50]Kasai H, Fukuda M, Watanabe S, Hayashi-Takagi A, Noguchi J (2010) Structural dynamics of dendritic spines in memory and cognition. Trends Neurosci 33: 121- 129. doi: 10.1016/j.tins.2010.01.001. PubMed: 20138375. 20138375 · DOI · Paper page
  47. [52]Nusser Z, Lujan R, Laube G, Roberts JDB, Molnar E et al. (1998) Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21: 545- 559. doi: 10.1016/S0896-6273(00)80565-6. PubMed: 9768841. 9768841 · DOI · Paper page
  48. [53]Ehlers MD (2000) Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting. Neuron 28: 511- 525. doi: 10.1016/S0896-6273(00)00129-X. PubMed: 11144360. 11144360 · DOI · Paper page

Cited by

Sorted by citations

Authors
Hazai, D., Szudoczki, R., Ding, J., Soderling, S. H., Weinberg, R. J., Sótonyi, P., & Rácz, B.
Affiliations
  • Magyar Agrár- és Élettudományi Egyetem (HU)
  • Duke University (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Rácz, Bence
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-09-25
Volume
8
Issue
9
Pages
e75248
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0075248
PMC
PMC3783472
OpenAlex
W2023402428
Cited by
22
References
6
Citations by year
2026: 1 · 2025: 1 · 2023: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 4
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion, other-oa)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UNC Libraries
Funders
  • Hungarian Scientific Research Fund (K83830, TÁMOP-4.2.1.B-11/2/KMR-2011-0003, TÁMOP-4.2.2.B-10/1)
  • Magyar Tudományos Akadémia
  • National Institutes of Health (NS059957)
  • National Institute of Neurological Disorders and Stroke (R01NS039444, NS-39444, R56NS059957, 2R56-NS059957, R01NS035527, NS-35527)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
hippocampal CA1, synaptic ultrastructure, dendritic spines, axon terminals, actin cytoskeleton remodeling, Arp2/3 complex, small GTPases, knockout mice, stratum radiatum, synaptic structure, memory
MeSH terms
Actins, Animals, Hippocampus, Microscopy, Electron, Synapses, Presynaptic Terminals, Mice, Knockout, Dendritic Spines, Wiskott-Aldrich Syndrome Protein Family, Mice

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