Skip to main content
SpringerLink
Log in

A Method to Regulate Cofilin Transport Using Optogenetics and Live Video Analysis

  • Chapter
  • First Online:
Video Bioinformatics

Part of the book series: Computational Biology ((COBO,volume 22))

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease, where early stages of learning and memory loss are associated with a pronounced loss of synapses and dendritic spines. The actin-severing protein cofilin regulates the remodeling of dendritic spines in neurons, which are small protrusions on the surface of dendrites that receive inputs from neighboring neurons. However, the underlying mechanisms that mediate this are unclear. Previous studies have reported that phosphorylation regulates cofilin activity, but not much is known about the spatiotemporal dynamics of cofilin in synapses and spines. Here, an optogenetic method was developed to modulate the activity of cofilin, and video bioinformatics tools were used to study cofilin transport in dendritic spines and its effects on synapses. Gaining further insight into the workings of cofilin in spines can lead to potential therapies that regulate synaptic connectivity in the brain. In this chapter, a light-inducible, multichannel, live video imaging system was used to track the localization of cofilin, regulate its activity, and modulate synaptic connectivity in cultured hippocampal neurons.

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 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

  1. Gervais F et al (2007) Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging 28(40):537–547

    Google Scholar 

  2. Palop JJ, Mucke L (2010) Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat Neurosci 13(7):812–818

    Article  Google Scholar 

  3. Scheff SW et al (2007) Synaptic alternations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 68(18):1501–1508

    Article  Google Scholar 

  4. Halpain S, Spencer K, Graber S (2005) Dynamics and pathology of dendritic spines. Prog Brain Res 147:29–37

    Article  Google Scholar 

  5. Ethell IM, Pasquale EB (2005) Molecular mechanisms of dendritic spine development and remodeling. Prog Neurobiol 75:161–205

    Article  Google Scholar 

  6. Bamburg JR et al (2010) ADF/Cofilin-actin rods in neurodegenerative diseases. Curr Alzheimer Res 7(3):241–250

    Article  Google Scholar 

  7. Rao A, Craig AM (2000) Signaling between the actin cytoskeleton and the postsynaptic density of dendritic spines. Hippocampus 10(5):527–541

    Article  Google Scholar 

  8. Sorra KE, Harris KM (2000) Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines. Hippocampus 10(5):501–511

    Article  Google Scholar 

  9. Hering H, Sheng M (2001) Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci 2(12):880–888

    Article  Google Scholar 

  10. Yuste R, Bonhoeffer T (2004) Genesis of dendritic spines: insights from ultra-structural and imaging studies. Nat Rev Neurosci 5(1):24–34

    Article  Google Scholar 

  11. Matsuzaki M et al (2001) Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci 4(11):1086–1092

    Article  Google Scholar 

  12. Segal M (2005) Dendritic spines and long-term plasticity. Nat Rev Neurosci 6(4):277–284

    Article  Google Scholar 

  13. Yasumatsu N et al (2008) Principles of long-term dynamics of dendritic spines. J Neurosci 28(50):13592–13608

    Article  Google Scholar 

  14. Matsuzaki M et al (2004) Structural basis of long-term potentiation in single dendritic spines. Nature 429(6993):761–766

    Article  Google Scholar 

  15. Okamoto K et al (2004) Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Nat Neurosci 7(10):1104–1112

    Article  Google Scholar 

  16. Zhou Q, Homma KJ, Poo MM (2004) Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron 44(5):749–757

    Article  Google Scholar 

  17. Zito K et al (2009) Rapid functional maturation of nanscent dendritic spines. Neuron 61(2):247–258

    Article  Google Scholar 

  18. Kasai H et al (2010) Structural dynamics of dendritic spines in memory and cognition. Trends Neurosci 33(3):121–129

    Article  Google Scholar 

  19. Takumi Y et al (1999) Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat Neurosci 2(7):618–624

    Article  Google Scholar 

  20. Racca C et al (2000) NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area. J Neurosci 20(7):2512–2522

    Google Scholar 

  21. Minamide LS et al (2000) Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function. Nat Cell Biol 2(9):628–636

    Article  Google Scholar 

  22. Fukazawa Y et al (2003) Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spines that is essential for late LTP maintenance in vivo. Neuron 38(3):447–460

    Article  Google Scholar 

  23. Andrianantoandro E, Pollard TD (2006) Mechanisms of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell 24(1):13–23

    Article  Google Scholar 

  24. Chan C, Beltzner CC, Pollard TD (2009) Cofilin dissociates Arp2/3 complex and branches from actin filaments. Curr Biol 19(7):537–545. (REPEAT OF 35)

    Google Scholar 

  25. Gungabissoon RA, Bamburg JR (2003) Regulation of growth cone actin dynamics by ADF/cofilin. J Histochem Cytochem 51(4):411–420

    Article  Google Scholar 

  26. Whiteman IT, Gervasio OL, Cullen KM et al (2009) Activated actin-depolymerizing factor/cofilin sequesters phosphorylated microtubule-associated protein during the assembly of Alzheimer-like neuritic cytoskeletal striations. J Neurosci 29(41):12994–13005

    Article  Google Scholar 

  27. Maloney MT et al (2005) Beta-secretase-cleaved amyloid precursor protein accumulates at actin inclusions induced in neurons by stress or amyloid beta: a feedforward mechanism for Alzheimer’s disease. J Neurosci 25(49):11313–11321

    Article  Google Scholar 

  28. Shankar GM et al (2007) Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci 27(11):2866–2875

    Article  Google Scholar 

  29. Hsieh H et al (2006) AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52(5):831–843

    Article  Google Scholar 

  30. Li S et al (2009) Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62(60):788–801

    Google Scholar 

  31. Pontrello CG et al (2012) Cofilin under control of β-arrestin2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning. PNAS

    Google Scholar 

  32. Condeelis J (2001) How is actin polymerization nucleated in vivo? Trends Cell Biol 11(7):288–293

    Article  Google Scholar 

  33. Sarmiere PD, Bamburg JR (2004) Regulation of the neuronal actin cytoskeleton by ADF/cofilin. J Neurobiol 58(1):103–117

    Article  Google Scholar 

  34. Yang N et al (1998) Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature 393(6687):809–812

    Article  Google Scholar 

  35. Gungabissoon RA, Bamburg JR (2003) Regulation of growth cone actin dynamics by ADF/cofilin. J Histochem Cytochem 51(4):411–420

    Article  Google Scholar 

  36. DesMarais V et al (2005) Cofilin takes the lead. J Cel Sci 118(Pt 1):19–26

    Article  Google Scholar 

  37. Bamburg JR (1999) Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol 15:185–230

    Article  Google Scholar 

  38. Shi Y et al (2009) Focal adhesion kinase acts downstream of EphB receptors to maintain mature dendritic spines by regulating cofilin activity. J Neurosci 29(25):8129–8142

    Article  Google Scholar 

  39. Bamburg JR (1999) Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol 15:185–230

    Article  Google Scholar 

  40. Condeelis J (2001) How is actin polymerization nucleated in vivo? Trends Cell Biol 11(7):288–293

    Article  Google Scholar 

  41. Sarmier PD, Bamburg JR (2004) Regulation of the neuronal actin cytoskeleton by ADF/cofilin. J Neurobiol 58(1):103–117

    Article  Google Scholar 

  42. Chan C, Beltzner CC, Pollard TD (2009) Cofilin dissociates Arp2/3 complex and branches from actin filaments. Curr Biol 19(7):537–545

    Article  Google Scholar 

  43. Arber S et al (1998) Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 393(6687):805–809

    Article  Google Scholar 

  44. Carlisle HJ et al (2008) SynGAP regulates steady-state and activity-dependent phosphorylation of cofilin. J Neurosci 28(50):13673–13683

    Article  Google Scholar 

  45. Quinlan EM, Halpain S (1996) Postsynaptic mechanisms for bidirectional control of MAP2 phosphorylation by glutamate receptors. Neuron 16(2):357–368

    Article  Google Scholar 

  46. Wang Y, Shibasaki F, Mizuno K (2005) Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot via calcineurin. J Biol Chem 280(13):12683–12689

    Article  Google Scholar 

  47. Wu YI, Hahn KM et al (2009) A genetically-encoded photoactivatable Rac controls the motility of living cells. Nature 461(7260):104–108

    Article  Google Scholar 

  48. Zahedi A et al (2013) Optogenetics to target actin-mediated synaptic loss in Alzheimer’s. In: Proceedings of SPIE 8586, optogenetics: optical methods for cellular control, vol 85860S

    Google Scholar 

  49. Elowitz MB, Surette MG, Wolf PE, Stock JB, Leibler S (1999) Protein mobility in the cytoplasm of Escherichia coli. J Bacteriol 1:197203

    Google Scholar 

  50. Chicon J et al (2012) Cofilin aggregation blocks intracellular trafficking and induces synaptic loss in hippocampal neurons. J Biol Chem 287:3919–3929

    Article  Google Scholar 

  51. Davis RC et al (2009) Mapping cofilin-actin rods in stressed hippocampal slices and the role of cdc42 in amyloid-beta-induced rods. J Alzheimers Dis 18(1):35–50

    Google Scholar 

Download references

Acknowledgment

This work was supported in part by the National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT) in Video Bioinformatics (DGE-0903667). Atena Zahedi and Vincent On are IGERT Fellows.

Author information

Authors and Affiliations

  1. Bioengineering Department, University of California Riverside, Riverside, CA, 92521, USA

    Atena Zahedi

  2. Electrical and Computer Engineering Department, University of California Riverside, Riverside, CA, 92521, USA

    Vincent On

  3. Biomedical Sciences Department, University of California Riverside, Riverside, CA, 92521, USA

    Iryna Ethell

Authors
  1. Atena Zahedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent On
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Iryna Ethell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iryna Ethell .

Editor information

Editors and Affiliations

  1. University of California, Riverside, California, USA

    Bir Bhanu

  2. University of California, Riverside, California, USA

    Prue Talbot

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Zahedi, A., On, V., Ethell, I. (2015). A Method to Regulate Cofilin Transport Using Optogenetics and Live Video Analysis. In: Bhanu, B., Talbot, P. (eds) Video Bioinformatics. Computational Biology, vol 22. Springer, Cham. https://doi.org/10.1007/978-3-319-23724-4_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-23724-4_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-23723-7

  • Online ISBN: 978-3-319-23724-4

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics

Search

Navigation