A FRET Sensor for Non-Invasive Imaging of Amyloid Formation in Vivo

Kaminski Schierle GS, Bertoncini CW, Chan FTS, van der Goot AT, Schwedler S, Skepper J, Schlachter S, van Ham T, Esposito A, Kumita JR, Nollen EAA, et al. (2011)
ChemPhysChem 12(3): 673-680.

Journal Article | Published | English

No fulltext has been uploaded

; ; ; ; ; ; ; ; ; ; ;
Misfolding and aggregation of amyloidogenic polypeptides lie at the root of many neurodegenerative diseases. Whilst protein aggregation can be readily studied in vitro by established biophysical techniques, direct observation of the nature and kinetics of aggregation processes taking place in vivo is much more challenging. We describe here, however, a Forster resonance energy transfer sensor that permits the aggregation kinetics of amyloidogenic proteins to be quantified in living systems by exploiting our observation that amyloid assemblies can act as energy acceptors for variants of fluorescent proteins. The observed lifetime reduction can be attributed to fluorescence energy transfer to intrinsic energy states associated with the growing amyloid species. Indeed, for alpha-synuclein, a protein whose aggregation is linked to Parkinson's disease, we have used this sensor to follow the kinetics of the self-association reactions taking place in vitro and in vivo and to reveal the nature of the ensuing aggregated species. Experiments were conducted in vitro, in cells in culture and in living Caenorhabditis elegans. For the latter the readout correlates directly with the appearance of a toxic phenotype. The ability to measure the appearance and development of pathogenic amyloid species in a living animal and the ability to relate such data to similar processes observed in vitro provides a powerful new tool in the study of the pathology of the family of misfolding disorders. Our study confirms the importance of the molecular environment in which aggregation reactions take place, highlighting similarities as well as differences between the processes occurring in vitro and in vivo, and their significance for defining the molecular physiology of the diseases with which they are associated.
Publishing Year

Cite this

Kaminski Schierle GS, Bertoncini CW, Chan FTS, et al. A FRET Sensor for Non-Invasive Imaging of Amyloid Formation in Vivo. ChemPhysChem. 2011;12(3):673-680.
Kaminski Schierle, G. S., Bertoncini, C. W., Chan, F. T. S., van der Goot, A. T., Schwedler, S., Skepper, J., Schlachter, S., et al. (2011). A FRET Sensor for Non-Invasive Imaging of Amyloid Formation in Vivo. ChemPhysChem, 12(3), 673-680.
Kaminski Schierle, G. S., Bertoncini, C. W., Chan, F. T. S., van der Goot, A. T., Schwedler, S., Skepper, J., Schlachter, S., van Ham, T., Esposito, A., Kumita, J. R., et al. (2011). A FRET Sensor for Non-Invasive Imaging of Amyloid Formation in Vivo. ChemPhysChem 12, 673-680.
Kaminski Schierle, G.S., et al., 2011. A FRET Sensor for Non-Invasive Imaging of Amyloid Formation in Vivo. ChemPhysChem, 12(3), p 673-680.
G.S. Kaminski Schierle, et al., “A FRET Sensor for Non-Invasive Imaging of Amyloid Formation in Vivo”, ChemPhysChem, vol. 12, 2011, pp. 673-680.
Kaminski Schierle, G.S., Bertoncini, C.W., Chan, F.T.S., van der Goot, A.T., Schwedler, S., Skepper, J., Schlachter, S., van Ham, T., Esposito, A., Kumita, J.R., Nollen, E.A.A., Dobson, C.M., Kaminski, C.F.: A FRET Sensor for Non-Invasive Imaging of Amyloid Formation in Vivo. ChemPhysChem. 12, 673-680 (2011).
Kaminski Schierle, Gabriele S., Bertoncini, Carlos W., Chan, Fiona T. S., van der Goot, Annemieke T., Schwedler, Stefanie, Skepper, Jeremy, Schlachter, Simon, van Ham, Tjakko, Esposito, Alessandro, Kumita, Janet R., Nollen, Ellen A. A., Dobson, Christopher M., and Kaminski, Clemens F. “A FRET Sensor for Non-Invasive Imaging of Amyloid Formation in Vivo”. ChemPhysChem 12.3 (2011): 673-680.
This data publication is cited in the following publications:
This publication cites the following data publications:

18 Citations in Europe PMC

Data provided by Europe PubMed Central.

ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function.
Murakami T, Qamar S, Lin JQ, Schierle GS, Rees E, Miyashita A, Costa AR, Dodd RB, Chan FT, Michel CH, Kronenberg-Versteeg D, Li Y, Yang SP, Wakutani Y, Meadows W, Ferry RR, Dong L, Tartaglia GG, Favrin G, Lin WL, Dickson DW, Zhen M, Ron D, Schmitt-Ulms G, Fraser PE, Shneider NA, Holt C, Vendruscolo M, Kaminski CF, St George-Hyslop P., Neuron 88(4), 2015
PMID: 26526393
Timing protein assembly in neurons.
Sauer M., Chem. Biol. 21(6), 2014
PMID: 24950101
Physicochemical properties of cells and their effects on intrinsically disordered proteins (IDPs).
Theillet FX, Binolfi A, Frembgen-Kesner T, Hingorani K, Sarkar M, Kyne C, Li C, Crowley PB, Gierasch L, Pielak GJ, Elcock AH, Gershenson A, Selenko P., Chem. Rev. 114(13), 2014
PMID: 24901537
Direct observations of amyloid β self-assembly in live cells provide insights into differences in the kinetics of Aβ(1-40) and Aβ(1-42) aggregation.
Esbjorner EK, Chan F, Rees E, Erdelyi M, Luheshi LM, Bertoncini CW, Kaminski CF, Dobson CM, Kaminski Schierle GS., Chem. Biol. 21(6), 2014
PMID: 24856820
Stages and conformations of the Tau repeat domain during aggregation and its effect on neuronal toxicity.
Kumar S, Tepper K, Kaniyappan S, Biernat J, Wegmann S, Mandelkow EM, Muller DJ, Mandelkow E., J. Biol. Chem. 289(29), 2014
PMID: 24825901
Biophysical groundwork as a hinge to unravel the biology of α-synuclein aggregation and toxicity.
Plotegher N, Greggio E, Bisaglia M, Bubacco L., Q. Rev. Biophys. 47(1), 2014
PMID: 24443929
Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology.
Michel CH, Kumar S, Pinotsi D, Tunnacliffe A, St George-Hyslop P, Mandelkow E, Mandelkow EM, Kaminski CF, Kaminski Schierle GS., J. Biol. Chem. 289(2), 2014
PMID: 24235150
Real-time probing of β-amyloid self-assembly and inhibition using fluorescence self-quenching between neighbouring dyes.
Quinn SD, Dalgarno PA, Cameron RT, Hedley GJ, Hacker C, Lucocq JM, Baillie GS, Samuel ID, Penedo JC., Mol Biosyst 10(1), 2014
PMID: 24170094
Cerebellar soluble mutant ataxin-3 level decreases during disease progression in Spinocerebellar Ataxia Type 3 mice.
Nguyen HP, Hubener J, Weber JJ, Grueninger S, Riess O, Weiss A., PLoS ONE 8(4), 2013
PMID: 23626768
A label-free, quantitative assay of amyloid fibril growth based on intrinsic fluorescence.
Pinotsi D, Buell AK, Dobson CM, Kaminski Schierle GS, Kaminski CF., Chembiochem 14(7), 2013
PMID: 23592254
Protein amyloids develop an intrinsic fluorescence signature during aggregation.
Chan FT, Kaminski Schierle GS, Kumita JR, Bertoncini CW, Dobson CM, Kaminski CF., Analyst 138(7), 2013
PMID: 23420088
Analysis of the native structure, stability and aggregation of biotinylated human lysozyme.
Ahn M, De Genst E, Kaminski Schierle GS, Erdelyi M, Kaminski CF, Dobson CM, Kumita JR., PLoS ONE 7(11), 2012
PMID: 23166837
Early amyloidogenic oligomerization studied through fluorescence lifetime correlation spectroscopy.
Paredes JM, Casares S, Ruedas-Rama MJ, Fernandez E, Castello F, Varela L, Orte A., Int J Mol Sci 13(8), 2012
PMID: 22949804
Imaging nanometer-sized α-synuclein aggregates by superresolution fluorescence localization microscopy.
Roberti MJ, Folling J, Celej MS, Bossi M, Jovin TM, Jares-Erijman EA., Biophys. J. 102(7), 2012
PMID: 22500760
ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism.
Murakami T, Yang SP, Xie L, Kawano T, Fu D, Mukai A, Bohm C, Chen F, Robertson J, Suzuki H, Tartaglia GG, Vendruscolo M, Kaminski Schierle GS, Chan FT, Moloney A, Crowther D, Kaminski CF, Zhen M, St George-Hyslop P., Hum. Mol. Genet. 21(1), 2012
PMID: 21949354

54 References

Data provided by Europe PubMed Central.

Biophotonic techniques for the study of malaria-infected red blood cells.
Mauritz JM, Esposito A, Tiffert T, Skepper JN, Warley A, Yoon YZ, Cicuta P, Lew VL, Guck JR, Kaminski CF., Med Biol Eng Comput 48(10), 2010
PMID: 20661776
Towards multiparametric fluorescent imaging of amyloid formation: studies of a YFP model of alpha-synuclein aggregation.
van Ham TJ, Esposito A, Kumita JR, Hsu ST, Kaminski Schierle GS, Kaminski CF, Dobson CM, Nollen EA, Bertoncini CW., J. Mol. Biol. 395(3), 2010
PMID: 19891973
Quantitative imaging of human red blood cells infected with Plasmodium falciparum.
Esposito A, Choimet JB, Skepper JN, Mauritz JM, Lew VL, Kaminski CF, Tiffert T., Biophys. J. 99(3), 2010
PMID: 20682274
Catalytic and chaperone-like functions in an intrinsically disordered protein associated with desiccation tolerance.
Chakrabortee S, Meersman F, Kaminski Schierle GS, Bertoncini CW, McGee B, Kaminski CF, Tunnacliffe A., Proc. Natl. Acad. Sci. U.S.A. 107(37), 2010
PMID: 20805515


0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®


PMID: 21308945
PubMed | Europe PMC

Search this title in

Google Scholar