Chasing the signaling run by tri-molecular time-lapse FRET microscopy

Kuo, Hsiang Ling; Ho, Pei Chuan; Huang, Shu-Ching; Chang, Nan Shan

doi:10.1038/s41420-018-0047-4

Cited by 15 publications

(38 citation statements)

References 34 publications

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“…Other functions may be also different between vHMM-HA and shorter HMM-HA. In addition, while CD44-p53 signals play a critical role in the cytoprotective effect of vHMM-HA, other HA-binding proteins, such as versican 39 , as well as other aspects of CD44, such as formation of molecular complexes 40 and picket fence 41 , may be involved in the cytoprotective effect or other function of vHMM-HA. Although these issues are beyond the scope of this study, our proteomic and transcriptomic data might be useful resources for addressing these questions.…”

Section: Discussionmentioning

confidence: 99%

Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties

et al. 2020

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Naked mole-rat (NMR), the longest-living rodent, produces very-high-molecular-mass hyaluronan (vHMM-HA), compared to other mammalian species. However, it is unclear if exceptional polymer length of vHMM-HA is important for longevity. Here, we show that vHMM-HA (>6.1 MDa) has superior cytoprotective properties compared to the shorter HMM-HA. It protects not only NMR cells, but also mouse and human cells from stressinduced cell-cycle arrest and cell death in a polymer length-dependent manner. The cytoprotective effect is dependent on the major HA-receptor, CD44. We find that vHMM-HA suppresses CD44 protein-protein interactions, whereas HMM-HA promotes them. As a result, vHMM-HA and HMM-HA induce opposing effects on the expression of CD44dependent genes, which are associated with the p53 pathway. Concomitantly, vHMM-HA partially attenuates p53 and protects cells from stress in a p53-dependent manner. Our results implicate vHMM-HA in anti-aging mechanisms and suggest the potential applications of vHMM-HA for enhancing cellular stress resistance.

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Section: Discussionmentioning

confidence: 99%

Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties

et al. 2020

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“…This involves de-phosphorylation of WWOX at Y33 and Y61, but increased phosphorylation at S14, in MOLT-4 T cells in five minutes or less in vitro [ 9 ]. Zfra activates Z cells probably via the membrane Hyal-2/WWOX/SMAD4 signaling [ 12 , 13 , 14 , 15 , 16 , 17 ]. Zfra binds to the membrane Hyal-2 as a receptor in spleen Z cells [ 6 ].…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Zfra4-10 or WWOX7-21 Peptide Induces Complex Formation of WWOX with Selective Protein Targets in Organs that Leads to Cancer Suppression and Spleen Cytotoxic Memory Z Cell Activation In Vivo

Wan

Wang

Chang

et al. 2020

Cancers

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Synthetic Zfra4-10 and WWOX7-21 peptides strongly suppress cancer growth in vivo. Hypothetically, Zfra4-10 binds to the membrane Hyal-2 of spleen Z cells and activates the Hyal-2/WWOX/SMAD4 signaling for cytotoxic Z cell activation to kill cancer cells. Stimulation of membrane WWOX in the signaling complex by a WWOX epitope peptide, WWOX7-21, is likely to activate the signaling. Here, mice receiving Zfra4-10 or WWOX7-21 peptide alone exhibited an increased binding of endogenous tumor suppressor WWOX with ERK, C1qBP, NF-κB, Iba1, p21, CD133, JNK1, COX2, Oct4, and GFAP in the spleen, brain, and/or lung which led to cancer suppression. However, when in combination, Zfra4-10 and WWOX7-21 reduced the binding of WWOX with target proteins and allowed tumor growth in vivo. In addition to Zfra4-10 and WWOX7-21 peptides, stimulating the membrane Hyal-2/WWOX complex with Hyal-2 antibody and sonicated hyaluronan (HAson) induced Z cell activation for killing cancer cells in vivo and in vitro. Mechanistically, Zfra4-10 binds to membrane Hyal-2, induces dephosphorylation of WWOX at pY33 and pY61, and drives Z cell activation for the anticancer response. Thus, Zfra4-10 and WWOX7-21 peptides, HAson, and the Hyal-2 antibody are of therapeutic potential for cancer suppression.

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“…The usage of a blue, yellow and red fluorophore was the most abundant application for triple-FRET studies, as it provides a good compromise between large Förster distances due to high spectral overlap, and enough differences in excitation and emission spectra to detect each one separately. Until now, no study circumvented the direct FRET between D-A2 for genetically encoded fluorophores (He et al, 2005;Sun et al, 2010;Pauker et al, 2012;Hoppe et al, 2013;Wallrabe et al, 2013;Kuo et al, 2018). Possibly, because corrections for cross-talk would be still necessary and because it provides an additional layer of information on how the two fluorophores are located relative to each other.…”

Section: Discussionmentioning

confidence: 99%

“…Most three-fluorophore FRET approaches in the mammalian field use a combination of fluorescent proteins that emit in the blue, yellow and red spectral region (Galperin et al, 2004;He et al, 2005;Seidel et al, 2010Seidel et al, , 2010Sun et al, 2010;Pauker et al, 2012;Fábián et al, 2013;Hoppe et al, 2013;Krause et al, 2013;Wallrabe et al, 2013;Woehler, 2013;Fried et al, 2014;Kastantin et al, 2017) or organic dyes as Cy-, Atto-or Alexa-chromophores (Hohng et al, 2004;Lee et al, 2010;Kastantin et al, 2017). Rarely, the intermediate fluorophore emits in the green spectral region (Hur et al, 2016;Kuo et al, 2018). One report demonstrates the close proximity of three proteins of interest by labelling one protein with a blue-emitting fluorophore, and the other two with the same yellow-emitting fluorophore (Yu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Three-fluorophore FRET enables the analysis of ternary protein association in living plant cells

Glöckner

Oven-Krockhaus

Rohr

et al. 2019

Preprint

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Integration of signalling on the cellular level is essential for the survival of organisms.Protein-protein interaction studies provide valuable insights in these signalling events.One of the best understood signalling pathways in plants is the brassinosteroid (BR) hormone signalling pathway, which is mediated by the receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) with its co-receptor BRI1-ASSOCIATED KINASE (BAK1). Both BRI1 and BAK1 have been shown to interact with RECEPTOR LIKE PROTEIN 44 (RLP44), which was implicated in cell wall integrity sensing by modulation of BL signalling. Here we provide evidence by quantitative in vivo three-fluorophore FRET-FLIM measurements, that RLP44, BRI1 and BAK1 form a trimeric complex in the plasma membrane of N. benthamiana leaf cells, with an estimated distance between them below 15 nm. The immune receptor FLAGELLIN SENSING 2 (FLS2), which is also a receptor-like kinase like BRI1, is not integrated in a similar complex with RLP44 and BAK1. Our study supports that BRI1 and FLS2 are localized in distinct nanodomains in the PM. As the fluorescence lifetime of the donor is monitored, our method circumvents the extensive calculations necessitated by intensity-based FRET interaction assays and thus provides a feasible base for studying the sub-compartmentalization in the plasma membrane of living plant cells with a nanoscale resolution.

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Chasing the signaling run by tri-molecular time-lapse FRET microscopy

Cited by 15 publications

References 34 publications

Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties

Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties

Therapeutic Zfra4-10 or WWOX7-21 Peptide Induces Complex Formation of WWOX with Selective Protein Targets in Organs that Leads to Cancer Suppression and Spleen Cytotoxic Memory Z Cell Activation In Vivo

Three-fluorophore FRET enables the analysis of ternary protein association in living plant cells

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