Skip to main content
SpringerLink
Log in

Role of Drebrin in Synaptic Plasticity

  • Chapter
  • First Online:
Drebrin

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1006))

Abstract

Synaptic plasticity underlies higher brain function such as learning and memory, and the actin cytoskeleton in dendritic spines composing excitatory postsynaptic sites plays a pivotal role in synaptic plasticity. In this chapter, we review the role of drebrin in the regulation of the actin cytoskeleton during synaptic plasticity, under long-term potentiation (LTP) and long-term depression (LTD). Dendritic spines have two F-actin pools, drebrin-decorated stable F-actin (DF-actin) and drebrin-free dynamic F-actin (FF-actin). Resting dendritic spines change their shape, but are fairly constant over time at steady state because of the presence of DF-actin. Accumulation of DF-actin is inversely regulated by the intracellular Ca2+ concentration. However, LTP and LTD stimulation induce Ca2+ influx through N-methyl-d-aspartate (NMDA) receptors into the potentiated spines, resulting in drebrin exodus via myosin II ATPase activation. The potentiated spines change to excited state because of the decrease in DF-actin and thus change their shape robustly. In LTP, the Ca2+ increase via NMDA receptors soon returns to the basal level, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression at the postsynaptic membrane is increased. The Ca2+ recovery and AMPAR increase coordinately induce the re-accumulation of DF-actin and change the dendritic spines from the excited state to steady state during LTP maintenance. During LTD, the prolonged intracellular Ca2+ increase inhibits the re-accumulation of DF-actin, resulting in facilitation of AMPAR endocytosis. Because of the positive feedback loop of the AMPAR decrease and drebrin re-accumulation inhibition, the dendritic spines are instable during LTD maintenance. Taken together, we propose the presence of resilient spines at steady state and plastic spines at excited state and discuss the physiological and pathological relevance of the two-state model to synaptic plasticity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abraham WC, Williams JM (2003) Properties and mechanisms of LTP maintenance. Neuroscientist 9:463–474

    Article  CAS  PubMed  Google Scholar 

  • Allison DW, Gelfand VI, Spector I, Craig AM (1998) Role of actin in anchoring postsynaptic receptors in cultured hippocampal neurons: differential attachment of NMDA versus AMPA receptors. J Neurosci 18:2423–2436

    CAS  PubMed  Google Scholar 

  • Aoki C, Sekino Y, Hanamura K, Fujisawa S, Mahadomrongkul V, Ren Y, Shirao T (2005) Drebrin A is a postsynaptic protein that localizes in vivo to the submembranous surface of dendritic sites forming excitatory synapses. J Comp Neurol 483:383–402

    Google Scholar 

  • Arai H, Sato K, Uto A, Yasumoto Y (1991) Effect of Transient cerebral ischemia in mongolian gerbils on synaptic vesicle protein (SVP-38) and developmentally regulated brain protein (drebrin). Neurosci Res Commun 9:143–150

    Google Scholar 

  • Asrican B, Lisman J, Otmakhov N (2007) Synaptic strength of individual spines correlates with bound Ca2+-calmodulin-dependent kinase II. J Neurosci 27:14007–14011

    Article  CAS  PubMed  Google Scholar 

  • Biou V, Brinkhaus H, Malenka RC, Matus A (2008) Interactions between drebrin and Ras regulate dendritic spine plasticity. Eur J Neurosci 27:2847–2859

    Article  PubMed  Google Scholar 

  • Cao F, Zhou Z, Pan X, Leung C, Xie W, Collingridge G, Jia Z (2017) Developmental regulation of hippocampal long-term depression by cofilin-mediated actin reorganization. Neuropharmacology 112:66–75

    Article  CAS  PubMed  Google Scholar 

  • Chimura T, Launey T, Yoshida N (2015) Calpain-mediated degradation of drebrin by excitotoxicity in vitro and in vivo. PLoS One 10:e0125119

    Google Scholar 

  • Correia SS, Bassani S, Brown TC, Lise MF, Backos DS, El-Husseini A, Passafaro M, Esteban JA (2008) Motor protein-dependent transport of AMPA receptors into spines during long-term potentiation. Nat Neurosci 11:457–466

    Article  CAS  PubMed  Google Scholar 

  • Dailey ME, Smith SJ (1996) The dynamics of dendritic structure in developing hippocampal slices. J Neurosci 16:2983–2994

    CAS  PubMed  Google Scholar 

  • Desmond NL, Levy WB (1983) Synaptic correlates of associative potentiation/depression: an ultrastructural study in the hippocampus. Brain Res 265:21–30

    Article  CAS  PubMed  Google Scholar 

  • Fischer M, Kaech S, Knutti D, Matus A (1998) Rapid actin-based plasticity in dendritic spines. Neuron 20:847–854

    Article  CAS  PubMed  Google Scholar 

  • Fukazawa Y, Saitoh Y, Ozawa F, Ohta Y, Mizuno K, Inokuchi K (2003) Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron 38:447–460

    Google Scholar 

  • Geraldo S, Khanzada UK, Parsons M, Chilton JK, Gordon-Weeks PR (2008) Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis. Nat Cell Biol 10:1181–1189

    Article  CAS  PubMed  Google Scholar 

  • Gordon-Alonso M, Rocha-Perugini V, Alvarez S, Ursa A, Izquierdo-Useros N, Martinez-Picado J, Munoz-Fernandez MA, Sanchez-Madrid F (2013) Actin-binding protein drebrin regulates HIV-1-triggered actin polymerization and viral infection. J Biol Chem 288:28382–28397

    Google Scholar 

  • Goslin K, Banker G (1989) Experimental observations on the development of polarity by hippocampal neurons in culture. J Cell Biol 108(4):1507–1516

    Google Scholar 

  • Halpain S (2000) Actin and the agile spine: how and why do dendritic spines dance? Trends Neurosci 23:141–146

    Article  CAS  PubMed  Google Scholar 

  • Harigaya Y, Shoji M, Shirao T, Hirai S (1996) Disappearance of actin-binding protein, drebrin, from hippocampal synapses in Alzheimer’s disease. J Neurosci Res 43(1):87–92

    Google Scholar 

  • Harris KM, Stevens JK (1989) Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J Neurosci 9:2982–2997

    CAS  PubMed  Google Scholar 

  • Haviv L, Gillo D, Backouche F, Bernheim-Groswasser A (2008) A cytoskeletal demolition worker: myosin II acts as an actin depolymerization agent. J Mol Biol 375:325–330

    Article  CAS  PubMed  Google Scholar 

  • Hayashi K, Shirao T (1999) Change in the shape of dendritic spines caused by overexpression of drebrin in cultured cortical neurons. J Neurosci 19:3918–3925

    CAS  PubMed  Google Scholar 

  • Hayashi K, Ishikawa R, Ye LH, He XL, Takata K, Kohama K, Shirao T (1996) Modulatory role of drebrin on the cytoskeleton within dendritic spines in the rat cerebral cortex. J Neurosci 16:7161–7170

    CAS  PubMed  Google Scholar 

  • Honkura N, Matsuzaki M, Noguchi J, Ellis-Davies GC, Kasai H (2008) The subspine organization of actin fibers regulates the structure and plasticity of dendritic spines. Neuron 57:719–729

    Article  CAS  PubMed  Google Scholar 

  • Kaech S, Banker G (2006) Culturing hippocampal neurons. Nat Protoc 1:2406–2415

    Article  CAS  PubMed  Google Scholar 

  • Knott GW, Holtmaat A, Wilbrecht L, Welker E, Svoboda K (2006) Spine growth precedes synapse formation in the adult neocortex in vivo. Nat Neurosci 9(9):1117–1124. Epub 2006 Aug 6

    Google Scholar 

  • Kobayashi C, Aoki C, Kojima N, Yamazaki H, Shirao T (2007) Drebrin a content correlates with spine head size in the adult mouse cerebral cortex. J Comp Neurol 503:618–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koganezawa N, Hanamura K, Sekino Y, Shirao T (2017) The role of drebrin in dendritic spines. Mol Cell Neurosci. doi:10.1016/j.mcn.2017.01.004

  • Kojima N, Hanamura K, Yamazaki H, Ikeda T, Itohara S, Shirao T (2010) Genetic disruption of the alternative splicing of drebrin gene impairs context-dependent fear learning in adulthood. Neuroscience 165:138–150

    Article  CAS  PubMed  Google Scholar 

  • Kojima N, Shirao T (2007) Synaptic dysfunction and disruption of postsynaptic drebrin-actin complex: a study of neurological disorders accompanied by cognitive deficits. Neurosci Res 58(1):1–5. Epub 2007 Feb 11

    Google Scholar 

  • Korn ED, Carlier MF, Pantaloni D (1987) Actin polymerization and ATP hydrolysis. Science 238(4827):638–644

    Google Scholar 

  • Kojima N, Yasuda H, Hanamura K, Ishizuka Y, Sekino Y, Shirao T (2016) Drebrin A regulates hippocampal LTP and hippocampus-dependent fear learning in adult mice. Neuroscience 324:218–226

    Article  CAS  PubMed  Google Scholar 

  • Lu W, Man H, Ju W, Trimble WS, MacDonald JF, Wang YT (2001) Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron 29:243–254

    Article  CAS  PubMed  Google Scholar 

  • Ma Q, Ruan YY, Xu H, Shi XM, Wang ZX, Hu YL (2015) Safflower yellow reduces lipid peroxidation, neuropathology, tau phosphorylation and ameliorates amyloid β-induced impairment of learning and memory in rats. Biomed Pharmacother 76:153–164. doi: 10.1016/j.biopha.2015.10.004. Epub 2015 Nov 19

  • Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5–21

    Article  CAS  PubMed  Google Scholar 

  • Maletic-Savatic M, Malinow R, Svoboda K (1999) Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283:1923–1927

    Article  CAS  PubMed  Google Scholar 

  • Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H (2004) Structural basis of long-term potentiation in single dendritic spines. Nature 429:761–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuzaki M, Ellis-Davies GC, Nemoto T, Miyashita Y, Iino M, Kasai H (2001) Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci 4:1086–1092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matus A, Ackermann M, Pehling G, Byers HR, Fujiwara K (1982) High actin concentrations in brain dendritic spines and postsynaptic densities. Proc Natl Acad Sci U S A 79:7590–7594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mikati MA, Grintsevich EE, Reisler E (2013) Drebrin-induced stabilization of actin filaments. J Biol Chem 288:19926–19938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizui T, Takahashi H, Sekino Y, Shirao T (2005) Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions. Mol Cell Neurosci 30:149–157

    Article  CAS  PubMed  Google Scholar 

  • Mizui T, Kojima N, Yamazaki H, Katayama M, Hanamura K, Shirao T (2009) Drebrin E is involved in the regulation of axonal growth through actin-myosin interactions. J Neurochem 109:611–622

    Article  CAS  PubMed  Google Scholar 

  • Mizui T, Sekino Y, Yamazaki H, Ishizuka Y, Takahashi H, Kojima N, Kojima M, Shirao T (2014) Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines. PLoS One 9:e85367

    Article  PubMed  PubMed Central  Google Scholar 

  • Mulkey RM, Endo S, Shenolikar S, Malenka RC (1994) Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression. Nature 369:486–488

    Article  CAS  PubMed  Google Scholar 

  • Murrell MP, Gardel ML (2012) F-actin buckling coordinates contractility and severing in a biomimetic actomyosin cortex. Proc Natl Acad Sci U S A 109:20820–20825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nusser Z, Lujan R, Laube G, Roberts JD, Molnar E, Somogyi P (1998) Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21(3):545–559

    Google Scholar 

  • Okamoto K, Nagai T, Miyawaki A, Hayashi Y (2004) Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Nat Neurosci 7:1104–1112

    Article  CAS  PubMed  Google Scholar 

  • Ouyang Y, Wong M, Capani F, Rensing N, Lee CS, Liu Q, Neusch C, Martone ME, Wu JY, Yamada K, Ellisman MH, Choi DW (2005) Transient decrease in F-actin may be necessary for translocation of proteins into dendritic spines. Eur J Neurosci 22:2995–3005

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrozzino JJ, Pozzo Miller LD, Connor JA (1995) Micromolar Ca2+ transients in dendritic spines of hippocampal pyramidal neurons in brain slice. Neuron 14:1223–1231

    Article  CAS  PubMed  Google Scholar 

  • Rex CS, Gavin CF, Rubio MD, Kramar EA, Chen LY, Jia Y, Huganir RL, Muzyczka N, Gall CM, Miller CA, Lynch G, Rumbaugh G (2010) Myosin IIb regulates actin dynamics during synaptic plasticity and memory formation. Neuron 67:603–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rocca DL, Amici M, Antoniou A, Blanco Suarez E, Halemani N, Murk K, McGarvey J, Jaafari N, Mellor JR, Collingridge GL, Hanley JG (2013) The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity. Neuron 79:293–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8(6):595–608. doi: 10.15252/emmm.201606210

  • Sekino Y, Tanaka S, Hanamura K, Yamazaki H, Sasagawa Y, Xue Y, Hayashi K, Shirao T (2006) Activation of N-methyl-D-aspartate receptor induces a shift of drebrin distribution: disappearance from dendritic spines and appearance in dendritic shafts. Mol Cell Neurosci 31:493–504

    Article  CAS  PubMed  Google Scholar 

  • Sharma S, Grintsevich EE, Hsueh C, Reisler E, Gimzewski JK (2012) Molecular cooperativity of drebrin1-300 binding and structural remodeling of F-actin. Biophys J 103:275–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shirao T, Hanamura K, Koganezawa N, Ishizuka Y, Yamazaki H, Sekino Y (2017) The role of drebrin in neurons. J Neurochem. doi:10.1111/jnc.13988

  • Sokal DM, Mason R, Parker TL (2000) Multi-neuronal recordings reveal a differential effect of thapsigargin on bicuculline- or gabazine-induced epileptiform excitability in rat hippocampal neuronal networks. Neuropharmacology 39:2408–2417

    Article  CAS  PubMed  Google Scholar 

  • Star EN, Kwiatkowski DJ, Murthy VN (2002) Rapid turnover of actin in dendritic spines and its regulation by activity. Nat Neurosci 5(3):239–246

    Google Scholar 

  • Takahashi H, Yamazaki H, Hanamura K, Sekino Y, Shirao T (2009) Activity of the AMPA receptor regulates drebrin stabilization in dendritic spine morphogenesis. J Cell Sci 122:1211–1219

    Article  CAS  PubMed  Google Scholar 

  • Takahashi H, Sekino Y, Tanaka S, Mizui T, Kishi S, Shirao T (2003) Drebrin-dependent actin clustering in dendritic filopodia governs synaptic targeting of postsynaptic density-95 and dendritic spine mor phogenesis. J Neurosci 23:6586–6595

    Google Scholar 

  • Takumi Y, Ramírez-León V, Laake P, Rinvik E, Ottersen OP (1999) Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat Neurosci 2(7):618–624

    Google Scholar 

  • Trachtenberg JT, Chen BE, Knott GW, Feng G, Sanes JR, Welker E, Svoboda K (2002) Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420:788–794

    Google Scholar 

  • Wang XB, Yang Y, Zhou Q (2007) Independent expression of synaptic and morphological plasticity associated with long-term depression. J Neurosci 27:12419–12429

    Article  CAS  PubMed  Google Scholar 

  • Wegner AM, Nebhan CA, Hu L, Majumdar D, Meier KM, Weaver AM, Webb DJ (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson CA, Tsuchida MA, Allen GM, Barnhart EL, Applegate KT, Yam PT, Ji L, Keren K, Danuser G, Theriot JA (2010) Myosin II contributes to cell-scale actin network treadmilling through network disassembly. Nature 465:373–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Worth DC, Daly CN, Geraldo S, Oozeer F, Gordon-Weeks PR (2013) Drebrin contains a cryptic F-actin-bundling activity regulated by Cdk5 phosphorylation. J Cell Biol 202:793–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yasumatsu N, Matsuzaki M, Miyazaki T, Noguchi J, Kasai H (2008) Principles of long-term dynamics of dendritic spines. J Neurosci 28:13592–13608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuste R (2015) The discovery of dendritic spines by Cajal. Front Neuroanat 9:18

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou Q, Homma KJ, Poo MM (2004) Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron 44:749–757

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann J, Falcke M (2014) Formation of transient lamellipodia. PLoS One 9:e87638

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan

    Yuko Sekino, Noriko Koganezawa, Toshiyuki Mizui & Tomoaki Shirao

  2. Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan

    Yuko Sekino

Authors
  1. Yuko Sekino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Noriko Koganezawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshiyuki Mizui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomoaki Shirao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuko Sekino .

Editor information

Editors and Affiliations

  1. Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Tomoaki Shirao

  2. Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

    Yuko Sekino

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Japan KK

About this chapter

Cite this chapter

Sekino, Y., Koganezawa, N., Mizui, T., Shirao, T. (2017). Role of Drebrin in Synaptic Plasticity. In: Shirao, T., Sekino, Y. (eds) Drebrin. Advances in Experimental Medicine and Biology, vol 1006. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56550-5_11

Download citation

Publish with us

Policies and ethics

Search

Navigation