Natural variation in ZmFBL41 confers banded leaf and sheath blight resistance in maize

Article metrics

Abstract

Rhizoctonia solani is a widely distributed phytopathogen that causes banded leaf and sheath blight in maize and sheath blight in rice. Here, we identified an F-box protein (ZmFBL41) that confers resistance to banded leaf and sheath blight through a genome-wide association study in maize. Rice overexpressing ZmFBL41 showed elevated susceptibility to R. solani. Two amino acid substitutions in this allele prevent its interaction with ZmCAD, which encodes the final enzyme in the monolignol biosynthetic pathway, resulting in the inhibition of ZmCAD degradation and, consequently, the accumulation of lignin and restriction of lesion expansion. Knocking out the ZmCAD-homologous gene OsCAD8B in rice enhanced susceptibility to R. solani. The results reveal a susceptibility mechanism in which R. solani targets the host proteasome to modify the secondary metabolism of the plant cell wall for its invasion. More importantly, it provides an opportunity to generate R. solani–resistant varieties of different plant species.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: GWAS for BLSB resistance in maize.
Fig. 2: Natural variations in ZmFBL41 were significantly associated with maize resistance to R. solani.
Fig. 3: Function of ZmFBL41 in BLSB resistance.
Fig. 4: ZmFBL41B73 targets and triggers degradation of ZmCAD.
Fig. 5: Function of CAD in R. solani resistance.
Fig. 6: Two amino acid substitutions in the LRR domain of ZmFBL41Chang7-2 stabilize ZmCAD by blocking protein–protein interactions.
Fig. 7: A model for ZmFBL41-mediated BLSB resistance.

Data availability

Data supporting the findings of this work are available within the paper and its Supplementary Information. All materials used in this study have been described in previous studies8,33,34. The RNA-sequencing data for all 368 inbred lines have been deposited in the NCBI Sequence Read Archive under accession code SRP026161. The genotype after imputation can be downloaded from http://www.maizego.org/Resources.html. The widely used mapping population, although not owned by us, can—to our knowledge—be accessed by any researcher through appropriate application. Most of the data are from the GenBank of CIMMYT (details in Supplementary Table 1), which are public available, others can be obtained from the National GenBank, Institute of Crop Germplasm Resources of Chinese Academy of Agricultural Sciences (CAAS, http://www.cgris.net) with an MTA. The researchers can also contact the founders of lines of the mapping population (J.Y., yjianbing@mail.hzau.edu.cn). Source data for Figs. 3a,c, 5,a,c,e and Supplementary Figs. 1a, 2c, 6e,f have been provided in Supplementary Table 8.

References

  1. 1.

    Wen, W., Brotman, Y., Willmitzer, L., Yan, J. & Fernie, A. R. Broadening our portfolio in the genetic improvement of maize chemical composition. Trends Genet. 32, 459–469 (2016).

  2. 2.

    Lu, G. et al. Quantitative trait loci mapping of maize yield and its components under different water treatments at flowering time. J. Integr. Plant Biol. 48, 1233–1243 (2006).

  3. 3.

    Xiao, Y., Liu, H., Wu, L., Warburton, M. & Yan, J. Genome-wide association studies in maize: praise and stargaze. Mol. Plant 10, 359–374 (2017).

  4. 4.

    Flint-Garcia, S., Thornsberry, J. & Buckler, E. Structure of linkage disequilibrium in plants. Annu. Rev. Plant Biol. 54, 357–374 (2003).

  5. 5.

    Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516–1517 (1996).

  6. 6.

    Visscher, P. M., Brown, M. A., McCarthy, M. I. & Yang, J. Five years of GWAS discovery. Am. J. Hum. Genet. 90, 7–24 (2012).

  7. 7.

    Tian, F. et al. Genome-wide association study of leaf architecture in the maize nested association mapping population. Nat. Genet. 43, 159–162 (2011).

  8. 8.

    Li, H. et al. Genome-wide association study dissects the genetic architecture of oil biosynthesis in maize kernels. Nat. Genet. 45, 43–50 (2013).

  9. 9.

    Si, L. et al. OsSPL13 controls grain size in cultivated rice. Nat. Genet. 48, 447–456 (2016).

  10. 10.

    Wang, X. et al. Genetic variation in ZmVPP1 contributes to drought tolerance in maize seedlings. Nat. Genet. 48, 1233–1241 (2016).

  11. 11.

    Yano, K. et al. Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice. Nat. Genet. 48, 927–934 (2016).

  12. 12.

    Li, W. et al. A natural allele of a transcription factor in rice confers broad-spectrum blast resistance. Cell 170, 114–126 (2017).

  13. 13.

    Ding, J. et al. Genome-wide association mapping reveals novel sources of resistance to northern corn leaf blight in maize. BMC Plant Biol. 15, 206 (2015).

  14. 14.

    Gowda, M. et al. Genome-wide association and genomic prediction of resistance to maize lethal necrosis disease in tropical maize germplasm. Theor. Appl. Genet. 128, 1957–1968 (2015).

  15. 15.

    Mammadov, J. et al. Combining powers of linkage and association mapping for precise dissection of QTL controlling resistance to gray leaf spot disease in maize (Zea mays L.). BMC Genom. 16, 916 (2015).

  16. 16.

    Tang, J. D., Perkins, A., Williams, W. P. & Warburton, M. L. Using genome-wide associations to identify metabolic pathways involved in maize aflatoxin accumulation resistance. BMC Genom. 16, 673 (2015).

  17. 17.

    Mahuku, G. et al. Combined linkage and association mapping identifies a major QTL (qRtsc8-1), conferring tar spot complex resistance in maize. Theor. Appl. Genet. 129, 1217–1229 (2016).

  18. 18.

    Zhao, M. et al. Quantitative trait loci for resistance to banded leaf and sheath blight in maize. Crop Sci. 46, 1039–1045 (2006).

  19. 19.

    Zheng, A. et al. The evolution and pathogenic mechanisms of the rice sheath blight pathogen. Nat. Commun. 4, 1424 (2013).

  20. 20.

    Sha, X. Y. & Zhu, L. H. Resistance of some rice varieties to sheath blight (ShB). Int. Rice Res. Newslett. 15, 7–8 (1989).

  21. 21.

    Li, Z., Pinson, S. R. M., Marchetti, M. A., Stansel, J. W. & Park, W. D. Characterization of quantitative trait loci (QTLs) in cultivated rice contributing to field resistance to sheath blight (Rhizoctonia solani). Theor. Appl. Genet. 91, 382–388 (1995).

  22. 22.

    Channamallikarjuna, V. et al. Identification of major quantitative trait loci qSBR11-1 for sheath blight resistance in rice. Mol. Breed. 25, 155–166 (2010).

  23. 23.

    Wang, Y., Pinson, S. R. M., Fjellstrom, R. G. & Tabien, R. E. Phenotypic gain from introgression of two QTL, qSB9-2 and qSB12-1, for rice sheath blight resistance. Mol. Breed. 30, 293–303 (2012).

  24. 24.

    Wang, H. et al. Rice WRKY4 acts as a transcriptional activator mediating defense responses toward Rhizoctonia solani, the causing agent of rice sheath blight. Plant Mol. Biol. 89, 157–171 (2015).

  25. 25.

    Richa, K. et al. Novel chitinase gene LOC_Os11g47510 from Indica rice Tetep provides enhanced resistance against sheath blight pathogen Rhizoctonia solani in rice. Front. Plant Sci. 8, 596 (2017).

  26. 26.

    Li, N. et al. OsASR2 regulates the expression of a defence-related gene, Os2H16, by targeting the GT-1 cis-element. Plant Biotechnol. J. 16, 771–783 (2018).

  27. 27.

    Furlan, G. et al. Changes in PUB22 ubiquitination modes triggered by MITOGEN-ACTIVATED PROTEIN KINASE3 dampen the immune response. Plant Cell 29, 726–745 (2017).

  28. 28.

    Tong, M. et al. E3 ligase SAUL1 serves as a positive regulator of PAMP‐triggered immunity and its homeostasis is monitored by immune receptor SOC3. New Phytol. 215, 1516–1532 (2017).

  29. 29.

    Hammoudi, V. et al. The Arabidopsis SUMO E3 ligase SIZ1 mediates the temperature dependent trade-off between plant immunity and growth. PLoS Genet. 14, e1007157 (2018).

  30. 30.

    Duplan, V. & Rivas, S. E3 ubiquitin-ligases and their target proteins during the regulation of plant innate immunity. Front. Plant Sci. 5, 42 (2014).

  31. 31.

    Wang, J. et al. Overexpression of VpEIFP1, a novel F-box/Kelch-repeat protein from wild Chinese Vitis pseudoreticulata, confers higher tolerance to powdery mildew by inducing thioredoxin z proteolysis. Plant Sci. 263, 142–155 (2017).

  32. 32.

    Huang, J., Zhu, C. & Li, X. SCFSNIPER4 controls the turnover of two redundant TRAF proteins in plant immunity. Plant J. 95, 504–515 (2018).

  33. 33.

    Yang, X. et al. Characterization of a global germplasm collection and its potential utilization for analysis of complex quantitative traits in maize. Mol. Breed. 28, 511–526 (2011).

  34. 34.

    Fu, J. et al. RNA sequencing reveals the complex regulatory network in the maize kernel. Nat. Commun. 4, 2832 (2013).

  35. 35.

    Jain, M. et al. F-Box proteins in rice. Genome-wide analysis, classification, temporal and spatial gene expression during panicle and seed development, and regulation by light and abiotic stress. Plant Physiol. 143, 1467–1483 (2007).

  36. 36.

    Kipreos, E. T. & Pagano, M. The F-box protein family. Genom. Biol. 1, reviews3002.1 (2000).

  37. 37.

    Zheng, N. et al. Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex. Nature 416, 703–709 (2002).

  38. 38.

    Skaar, J. R., Pagan, J. K. & Pagano, M. Mechanisms and function of substrate recruitment by F-box proteins. Nat. Rev. Mol. Cell Biol. 14, 369–381 (2013).

  39. 39.

    Xu, C. et al. Degradation of MONOCULM 1 by APC/CTAD1 regulates rice tillering. Nat. Commun. 3, 750 (2012).

  40. 40.

    Jun, S. Y. et al. The enzyme activity and substrate specificity of two major cinnamyl alcohol dehydrogenases in sorghum (Sorghum bicolor), SbCAD2 and SbCAD4. Plant Physiol. 174, 2128–2145 (2017).

  41. 41.

    Chezem, W. R., Memon, A., Li, F., Weng, J. & Clay, N. K. SG2-type R2R3-MYB transcription factor MYB15 controls defense-induced lignification and basal immunity in Arabidopsis. Plant Cell 29, 1907–1926 (2017).

  42. 42.

    Underwood, W. The plant cell wall: a dynamic barrier against pathogen invasion. Front. Plant Sci. 3, 85 (2012).

  43. 43.

    Malinovsky, F. G., Fangel, J. U. & Willats, W. G. The role of the cell wall in plant immunity. Front. Plant Sci. 5, 178 (2014).

  44. 44.

    Bellincampi, D., Cervone, F. & Lionetti, V. Plant cell wall dynamics and wall-related susceptibility in plant-pathogen interactions. Front. Plant Sci. 5, 228 (2014).

  45. 45.

    Escudero, V. et al. Alteration of cell wall xylan acetylation triggers defense responses that counterbalance the immune deficiencies of plants impaired in the β‐subunit of the heterotrimeric G‐protein. Plant J. 92, 386–399 (2017).

  46. 46.

    Lionetti, V. et al. Three pectin methylesterase inhibitors protect cell wall integrity for Arabidopsis immunity to Botrytis. Plant Physiol. 173, 1844–1863 (2017).

  47. 47.

    Bacete, L., Melida, H., Miedes, E. & Molina, A. Plant cell wall-mediated immunity: cell wall changes trigger disease resistance responses. Plant J. 93, 614–636 (2018).

  48. 48.

    Kubicek, C. P., Starr, T. L. & Glass, N. L. Plant cell wall-degrading enzymes and their secretion in plant-pathogenic fungi. Annu. Rev. Phytopathol. 52, 427–451 (2014).

  49. 49.

    Paccanaro, M. C. et al. Synergistic effect of different plant cell wall-degrading enzymes is important for virulence of Fusarium graminearum. Mol. Plant Microbe Interact. 30, 886–895 (2017).

  50. 50.

    Zhu, X. et al. Silencing PsKPP4, a MAP kinase kinase kinase gene, reduces pathogenicity of the stripe rust fungus. Mol. Plant Pathol. 19, 2590–2602 (2018).

  51. 51.

    Lakshman, D. K. et al. Proteomic investigation of Rhizoctonia solani AG4 identifies secretome and mycelial proteins with roles in plant cell wall degradation and virulence. J. Agric. Food Chem. 64, 3101–3110 (2016).

  52. 52.

    Wibberg, D. et al. Genome analysis of the sugar beet pathogen Rhizoctonia solani AG2-2IIIB revealed high numbers in secreted proteins and cell wall degrading enzymes. BMC Genom. 17, 245 (2016).

  53. 53.

    Boerjan, W., Ralph, J. & Baucher, M. Lignin biosynthesis. Annu. Rev. Plant Biol. 54, 519–546 (2003).

  54. 54.

    Weng, J. K. & Chapple, C. The origin and evolution of lignin biosynthesis. New Phytol. 187, 273–285 (2010).

  55. 55.

    Ma, Q., Zhu, H. & Qiao, M. Contribution of both lignin content and sinapyl monomer to disease resistance in tobacco. Plant Pathol. 67, 642–650 (2018).

  56. 56.

    Wang, X. et al. IDL6‐HAE/HSL2 impacts pectin degradation and resistance to Pseudomonas syringae pv tomato DC3000 in Arabidopsis leaves. Plant J. 89, 250–263 (2017).

  57. 57.

    Lechner, E., Achard, P., Vansiri, A., Potuschak, T. & Genschik, P. F-box proteins everywhere. Curr. Opin. Plant Biol. 9, 631–638 (2006).

  58. 58.

    Somers, D. E. & Fujiwara, S. Thinking outside the F-box: novel ligands for novel receptors. Trends Plant Sci. 14, 206–213 (2009).

  59. 59.

    Thines, B. et al. JAZ repressor proteins are targets of the SCFCOI1 complex during jasmonate signaling. Nature 448, 661–665 (2007).

  60. 60.

    Piisilä, M. et al. The F-box protein MAX2 contributes to resistance to bacterial phytopathogens in Arabidopsis thaliana. BMC Plant Biol. 15, 53 (2015).

  61. 61.

    Gou, M. et al. The F-box protein CPR1/CPR30 negatively regulates R protein SNC1 accumulation. Plant J. 69, 411–420 (2012).

  62. 62.

    Gou, M. et al. An F-box gene, CPR30, functions as a negative regulator of the defense response in Arabidopsis. Plant J. 60, 757–770 (2009).

  63. 63.

    Kim, H. S. & Delaney, T. P. Arabidopsis SON1 is an F-box protein that regulates a novel induced defense response independent of both salicylic acid and systemic acquired resistance. Plant Cell 14, 1469–1482 (2002).

  64. 64.

    Cao, Y. et al. Overexpression of a rice defense-related F-box protein gene OsDRF1 in tobacco improves disease resistance through potentiation of defense gene expression. Physiol. Plant. 134, 440–452 (2008).

  65. 65.

    Jia, F., Wu, B., Li, H., Huang, J. & Zheng, C. Genome-wide identification and characterization of F-box family in maize. Mol. Genet. Genom. 288, 559–577 (2013).

  66. 66.

    Park, C. H. et al. The Magnaporthe oryzae effector AvrPiz-t targets the RING E3 ubiquitin ligase APIP6 to suppress pathogen-associated molecular pattern-triggered immunity in rice. Plant Cell 24, 4748–4762 (2012).

  67. 67.

    Gonzalez-Lamothe, R. et al. The U-box protein CMPG1 is required for efficient activation of defense mechanisms triggered by multiple resistance genes in tobacco and tomato. Plant Cell 18, 1067–1083 (2006).

  68. 68.

    Bos, J. I. et al. Phytophthora infestans effector AVR3a is essential for virulence and manipulates plant immunity by stabilizing host E3 ligase CMPG1. Proc. Natl Acad. Sci. USA 107, 9909–9914 (2010).

  69. 69.

    Gilroy, E. M. et al. CMPG1-dependent cell death follows perception of diverse pathogen elicitors at the host plasma membrane and is suppressed by Phytophthora infestans RXLR effector AVR3a. New Phytol. 190, 653–666 (2011).

  70. 70.

    Chandrasekaran, J. et al. Development of broad virus resistance in non‐transgenic cucumber using CRISPR/Cas9 technology. Mol. Plant Pathol. 17, 1140–1153 (2016).

  71. 71.

    Jia, H. et al. Genome editing of the disease susceptibility gene CsLOB1 in citrus confers resistance to citrus canker. Plant Biotechnol. J. 15, 817–823 (2017).

  72. 72.

    Zhang, Y. et al. Simultaneous modification of three homoeologs of TaEDR1 by genome editing enhances powdery mildew resistance in wheat. Plant J. 91, 714–724 (2017).

  73. 73.

    Bradbury, P. J. et al. TASSEL: software for association mapping of complex traits in diverse samples. Bioinformatics 23, 2633–2635 (2007).

  74. 74.

    Chen, S., Songkumarn, P., Liu, J. & Wang, G. A versatile zero background T-vector system for gene cloning and functional genomics. Plant Physiol. 150, 1111–1121 (2009).

  75. 75.

    Yang, F. et al. Functional analysis of the GRMZM2G174449 promoter to identify Rhizoctonia solani-inducible cis-elements in maize. BMC Plant Biol. 17, 233 (2017).

  76. 76.

    Ma, X. & Liu, Y.-G. CRISPR/Cas9-based multiplex genome editing in monocot and dicot plants. Curr. Protoc. Mol. Biol. 115, 31.6.1–31.6.21 (2016).

Download references

Acknowledgements

We thank B. Liu and Y. Zhang from Shandong Agricultural University for seed propagation of maize transposon-insertion lines. This study was supported by the National Key Research and Development Program of China (2016YFD0101003 and 2016YFD0100903), the National Natural Science Foundation of China (31601279), the Key Research and Development Program of Shandong Province (2017GNC10104 and 2018GNC110018) and the Shandong Modern Agricultural Technology and Industry system (SDAIT-17-06).

Author information

N.L. inoculated the maize population, resequenced ZmFBL41, carried out the functional analysis of ZmFBL41 and ZmCAD, screened ZmFBL41-interacting proteins, carried out the expression analysis of ZmFBL41 and PR genes, measured the lignin content and wrote the paper. B.L. studied the degradation of ZmCAD and measured the lignin content. H.W. analyzed the GWAS data. X.L. inoculated the maize population. F.Y. studied the degradation of ZmCAD and constructed the OsCAD8B knockout line. X.D. analyzed the raw data. J.Y. provided the maize inbred lines and SNP data platform. Z.C. designed the experiments and wrote the paper.

Correspondence to Zhaohui Chu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Integrated supplementary information

Supplementary Fig. 1 Phenotypic variation in maize BLSB resistance in the natural-variation population.

(a) Distribution of lesion length in different maize inbred lines inoculated with R. solani. (b) Box-plot of lesion lengths from different origins. Center values are medians, solid lines indicate variability outside the upper and lower quartiles, and dots denote outliers. (c) Quantile-quantile plot for the GWAS under a general linear model (GLM). Statistical significance was determined by a two-sided t-test. TST, tropical or subtropical lines; NSS, non-stiff stalk; SS, stiff stalk.

Supplementary Fig. 2 Correlation analysis between lesion length and disease index from 10 maize lines inoculated with R. solani.

(a) Disease symptoms of SH and RH lines after inoculation with R. solani in the field. Scale bars, 10 cm. (b) Lesion length measured at 7 dpi in the field. Five SH and five RH lines were used and 5 plants of each line were measured. Independent experiments were repeated three times. (c) Disease index counted at 14 dpi in the field. Five SH and five RH lines were used and 10 plants of each line were measured. Independent experiments were repeated five times. In box plots, center values are medians, solid lines indicate variability outside the upper and lower quartiles, and dots denote outliers.

Supplementary Fig. 3 Structure and subcellular localization of ZmFBL41.

(a) A schematic diagram of the ZmFBL41 protein. The F-box and LRR domains are indicated. (b) ZmFBL41 is localized to the cytoplasm of N. benthamiana leaf cells. Scale bars, 50 μm. Localization is representative of three independent experiments.

Supplementary Fig. 4 Evaluation of ZmFBL41 overexpression lines and transposon-insertion line.

(a) Schematic of Mutator insertion relative to ZmFBL41 in maize line W22. Protein-coding regions are indicated as red bars. UTRs are indicated as white bars. The Mutator insertion is indicated by a blue triangle. The primers (F1, R1 and TIR-F) used for PCR of ZmFBL41 are indicated. (b) Identification of the zmfbl41 transposon-insertion line by PCR. See also Supplementary Fig. 8h. (c) Detection of ZmFBL41 gene expression in the zmfbl41 insertion line by qRT-PCR. In box plots, center values are medians and solid lines indicate variability outside the upper and lower quartiles. Statistical significance was determined by a two-sided t-test. Independent experiments were repeated five times. (d) Identification of ZmFBL41-overexpressing lines by RT-PCR. Gel is representative of three independent experiments. See also Supplementary Fig. 8i.

Supplementary Fig. 5 ZmFBL41 interacts with ZmSKP1 protein.

(a) A schematic diagram of ZmFBL41B73 and the truncations used for constructing bait vectors. (b) Y2H assay indicates that the interaction of ZmFBL41B73 and ZmSKP1-1 depends on the F-box domain. -WL, medium lacking Trp and Leu, -WLHA, medium lacking Trp, Leu, His and adenine. The images are representative of three independent experiments. (c) ZmFBL41B73 interacts with ZmSKP1-1 in a Co-IP assay. The ZmFBL41B73-HA or ZmFBL41B73ΔLRR-HA and ZmSKP1-1-Myc proteins were co-expressed in N. benthamiana leaves. Co-IP was carried out with an antibody to Myc, and the proteins were analysed by using Western blotting with the anti-HA (for ZmFBL41B73 and ZmFBL41B73ΔLRR), and anti-Myc (for ZmSKP1-1) antibodies. Blot is representative of three independent experiments. See also Supplementary Fig. 8j. (d) BiFC assay shows the ZmFBL41B73-ZmSKP1-1 interaction in N. benthamiana leaf cells. Scale bars, 50 μm. The images are representative of three independent experiments.

Supplementary Fig. 6 Identification of zmcad transposon-insertion line and OsCAD8B knockout transgenic lines.

(a) Schematic of Mutator insertion relative to ZmCAD in maize line W22. Protein-coding regions are indicated by red bars. The Mutator insertion is indicated by a blue triangle. The primers (F2, R2 and TIR-F) used for PCR of ZmCAD are indicated. (b) Identification of the zmcad transposon-insertion line by PCR. See also Supplementary Fig. 8k. (c) The target site designed to knock out the OsCAD8B gene by the CRISPR/Cas9 system. (d) Verification of knockout lines by PCR-based sequencing. A transgenic line (abbreviated as OsCAD8BKO) for OsCAD8B knockout was generated from the Zhonghua 11 genetic background. (e) Comparison of the plant height between the wild-type and the OsCAD8BKO line. 10 single 10-day-old seedlings of WT and OsCAD8BKO were measured. Scale bars, 4 cm. Independent experiments were repeated three times. (f) Determination of lignin content in the OsCAD8BKO line. 10 single plants of WT and OsCAD8BKO were measured. Independent experiments were repeated three times. In box plots, center values are medians and solid lines indicate variability outside the upper and lower quartiles. Statistical significance was determined by a two-sided t-test.

Supplementary Fig. 7 Sequence comparison of the LRR domains of ZmFBL41 between B73 and Chang7-2.

(a) Comparison of the B73 and Chang7-2 LRR domain CDS sequences. (b) Amino acid sequences of the LRR domains of B73 and Chang7-2. Identical bases are highlighted in black.

Supplementary Fig. 8 Raw blot and gel images related to main figures and Supplementary Figs.

(a) Western blots related to Fig. 4b. (b) Western blots related to Fig. 4d. (c) Western blots related to Fig. 4e. (d) Western blots related to Fig. 4f. (e) Western blots related to Fig. 6b. (f) Western blots related to Fig. 6c. (g) Western blots related to Fig. 6d. (h) Gel images related to Supplementary Fig. 4b. (i) Gel images related to Supplementary Fig. 4d. (j) Western blots related to Supplementary Fig. 5c. (k) Gel images related to Supplementary Fig. 6b.

Supplementary information

Supplementary Information

Supplementary Figs. 1–8

Reporting Summary

Supplementary Tables

Supplementary Tables 1–8

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark