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PatU3 plays a central role in coordinating cell division and differentiation in pattern formation of filamentous cyanobacterium Nostoc sp. PCC 7120

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Abstract

Spatial periodic signal for cell differentiation in some multicellular organisms is generated according to Turing’s principle for pattern formation. How a dividing cell responds to the signal of differentiation is addressed with the filamentous cyanobacterium Nostoc sp. PCC 7120, which forms the patterned distribution of heterocysts. We show that differentiation of a dividing cell was delayed until its division was completed and only one daughter cell became heterocyst. A mutant of patU3, which encodes an inhibitor of heterocyst formation, showed no such delay and formed heterocyst pairs from the daughter cells of cell division or dumbbell-shaped heterocysts from the cells undergoing cytokinesis. The patA mutant, which forms heterocysts only at the filament ends, restored intercalary heterocysts by a single nucleotide mutation of patU3, and double mutants of patU3/patA and patU3/hetF had the phenotypes of the patU3 mutant. We provide evidence that HetF, which can degrade PatU3, is recruited to cell divisome through its C-terminal domain. A HetF mutant with its N-terminal peptidase domain but lacking the C-terminal domain could not prevent the formation of heterocyst pairs, suggesting that the divisome recruitment of HetF is needed to sequester HetF for the delay of differentiation in dividing cells. Our study demonstrates that PatU3 plays a key role in cell-division coupled control of differentiation.

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References

  • Aravind, L., and Koonin, E.V. (2002). Classification of the caspase-hemoglobinase fold: detection of new families and implications for the origin of the eukaryotic separins. Proteins 46, 355–367.

    PubMed  CAS  Google Scholar 

  • Bailles, A., Gehrels, E.W., and Lecuit, T. (2022). Mechanochemical principles of spatial and temporal patterns in cells and tissues. Annu Rev Cell Dev Biol 38, 321–347.

    PubMed  CAS  Google Scholar 

  • Black, T.A., Cai, Y., and Wolk, C.P. (1993). Spatial expression and autoregulation of hetR, a gene involved in the control of heterocyst development in Anabaena. Mol Microbiol 9, 77–84.

    PubMed  CAS  Google Scholar 

  • Blatch, G.L., and Lässle, M. (1999). The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. Bioessays 21, 932–939.

    PubMed  CAS  Google Scholar 

  • Buikema W.J., and Haselkorn, R. (1991). Characterization of a gene controlling heterocyst differentiation in the cyanobacterium Anabaena 7120. Genes Dev 5, 321–330.

    PubMed  CAS  Google Scholar 

  • Buikema, W.J., and Haselkorn, R. (2001). Expression of the Anabaena hetR gene from a copper-regulated promoter leads to heterocyst differentiation under repressing conditions. Proc Natl Acad Sci USA 98, 2729–2734.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Claessen, D., Rozen, D.E., Kuipers, O.P., Søgaard-Andersen, L., and van Wezel, G.P. (2014). Bacterial solutions to multicellularity: a tale of biofilms, filaments and fruiting bodies. Nat Rev Microbiol 12, 115–124.

    PubMed  CAS  Google Scholar 

  • Di Patti, F., Lavacchi, L., Arbel-Goren, R., Schein-Lubomirsky, L., Fanelli, D., and Stavans, J. (2018). Robust stochastic Turing patterns in the development of a one-dimensional cyanobacterial organism. PLoS Biol 16, e2004877.

    PubMed  PubMed Central  Google Scholar 

  • Du, Y., Zhang, H., Wang, H., Wang, S., Lei, Q., Li, C., Kong, R., and Xu, X. (2020). Expression from DIF1-motif promoters of hetR and patS is dependent on HetZ and modulated by PatU3 during heterocyst differentiation. PLoS ONE 15, e0232383.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Elhai, J., and Khudyakov, I. (2018). Ancient association of cyanobacterial multicellularity with the regulator HetR and an RGSGR pentapeptide-containing protein (PatX). Mol Microbiol 110, 931–954.

    PubMed  CAS  Google Scholar 

  • Gierer, A., and Meinhardt, H. (1972). A theory of biological pattern formation. Kybernetik 12, 30–39.

    PubMed  CAS  Google Scholar 

  • Haselkorn, R. (1998). How cyanobacteria count to 10. Science 282, 891–892.

    PubMed  CAS  Google Scholar 

  • Herrero, A., and Flores, E. (2019). Genetic responses to carbon and nitrogen availability in Anabaena. Environ Microbiol 21, 1–17.

    PubMed  CAS  Google Scholar 

  • Herrero, A., Stavans, J., and Flores, E. (2016). The multicellular nature of filamentous heterocyst-forming cyanobacteria. FEMS Microbiol Rev 40, 831–854.

    PubMed  CAS  Google Scholar 

  • Hu, H.X., Jiang, Y.L., Zhao, M.X., Cai, K., Liu, S., Wen, B., Lv, P., Zhang, Y., Peng, J., Zhong, H., et al. (2015). Structural insights into HetR-PatS interaction involved in cyanobacterial pattern formation. Sci Rep 5, 16470.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Huang, X., Dong, Y., and Zhao, J. (2004). HetR homodimer is a DNA-binding protein required for heterocyst differentiation, and the DNA-binding activity is inhibited by PatS. Proc Natl Acad Sci USA 101, 4848–4853.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Kim, H., and Bressloff, P.C. (2020). Stochastic Turing pattern formation in a model with active and passive transport. Bull Math Biol 82, 144.

    PubMed  Google Scholar 

  • Kim, Y., Ye, Z., Joachimiak, G., Videau, P., Young, J., Hurd, K., Callahan, S.M., Gornicki, P., Zhao, J., Haselkorn, R., et al. (2013). Structures of complexes comprised of Fischerella transcription factor HetR with Anabaena DNA targets. Proc Natl Acad Sci USA 110, E1716–E1723.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Landge, A.N., Jordan, B.M., Diego, X., and Müller, P. (2020). Pattern formation mechanisms of self-organizing reaction-diffusion systems. Dev Biol 460, 2–11.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Lehner, J., Berendt, S., Dörsam, B., Pérez, R., Forchhammer, K., and Maldener, I. (2013). Prokaryotic multicellularity: a nanopore array for bacterial cell communication. FASEB J 27, 2293–2300.

    PubMed  CAS  Google Scholar 

  • Li, C., Zhang, H., Du, Y., Zhang, W., and Xu, X. (2021). Effects of PatU3 peptides on cell size and heterocyst frequency of Anabaena sp. strain PCC 7120. J Bacteriol 203, e0010821.

    PubMed  Google Scholar 

  • Liang, J., Scappino, L., and Haselkorn, R. (1992). The patA gene product, which contains a region similar to CheY of Escherichia coli, controls heterocyst pattern formation in the cyanobacterium Anabaena 7120. Proc Natl Acad Sci USA 89, 5655–5659.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Liu, J., Xing, W.Y., Zhang, J.Y., Zeng, X., Yang, Y., and Zhang, C.C. (2021). Functions of the essential gene mraY in cellular morphogenesis and development of the filamentous cyanobacterium Anabaena PCC 7120. Front Microbiol 12.

  • Liu, J., Xing, W.Y., Liu, B., and Zhang, C.C. (2023). Three-dimensional coordination of cell-division site positioning in a filamentous cyanobacterium. PNAS Nexus 2, pgac307.

    PubMed  Google Scholar 

  • Makarova, K.S., Koonin, E.V., Haselkorn, R., and Galperin, M.Y. (2006). Cyanobacterial response regulator PatA contains a conserved N-terminal domain (PATAN) with an alpha-helical insertion. Bioinformatics 22, 1297–1301.

    PubMed  CAS  Google Scholar 

  • Meinhardt, H., and Gierer, A. (2000). Pattern formation by local self-activation and lateral inhibition. BioEssays 22, 753–760.

    PubMed  CAS  Google Scholar 

  • Mitchison, G.J., and Wilcox, M. (1972). Rule governing cell division in Anabaena. Nature 239, 110–111.

    Google Scholar 

  • Miyagishima, S., Wolk, C.P., and Osteryoung, K.W. (2005). Identification of cyanobacterial cell division genes by comparative and mutational analyses. Mol Microbiol 56, 126–143.

    PubMed  CAS  Google Scholar 

  • Muñoz-García, J., and Ares, S. (2016). Formation and maintenance of nitrogen-fixing cell patterns in filamentous cyanobacteria. Proc Natl Acad Sci USA 113, 6218–6223.

    PubMed  PubMed Central  Google Scholar 

  • Refahi, Y., Brunoud, G., Farcot, E., Jean-Marie, A., Pulkkinen, M., Vernoux, T., and Godin, C. (2016). A stochastic multicellular model identifies biological watermarks from disorders in self-organized patterns of phyllotaxis. eLife 5, e14093.

    PubMed  PubMed Central  Google Scholar 

  • Reinitz, J. (2012). Pattern formation. Nature 482, 464.

    PubMed  CAS  Google Scholar 

  • Rippka, R., Deruelles, J., Waterbury, J.B., Herdman, M., and Stanier, R.Y. (1979). Generic assignments, strain histories and properties of pure cultures of cyanobacteria. Microbiology 111.

  • Risser, D.D., and Callahan, S.M. (2008). HetF and PatA control levels of HetR in Anabaena sp. strain PCC 7120. J Bacteriol 190, 7645–7654.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Risser, D.D., Wong, F.C.Y., and Meeks, J.C. (2012). Biased inheritance of the protein PatN frees vegetative cells to initiate patterned heterocyst differentiation. Proc Natl Acad Sci USA 109, 15342–15347.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Schweisguth, F., and Corson, F. (2019). Self-organization in pattern formation. Dev Cell 49, 659–677.

    CAS  Google Scholar 

  • Torres-Sanchez, A., Gomez-Gardenes, J., and Falo, F. (2015). An integrative approach for modeling and simulation of heterocyst pattern formation in cyanobacteria filaments. PLoS Comput Biol 11, e1004129.

    PubMed  PubMed Central  Google Scholar 

  • Turing, A.M. (1952). The chemical basis of morphogenesis. Phil Trans R Soc Lond B 237, 37–72.

    Google Scholar 

  • Valladares, A., Velazquez-Suarez, C., and Herrero, A. (2020). Interactions of PatA with the divisome during heterocyst differentiation in Anabaena. mSphere 5, e00188–20.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Videau, P., Rivers, O.S., Tom, S.K., Oshiro, R.T., Ushijima, B., Swenson, V.A., Philmus, B., Gaylor, M.O., and Cozy, L.M. (2018). The hetZ gene indirectly regulates heterocyst development at the level of pattern formation in Anabaena sp. strain PCC 7120. Mol Microbiol 109, 91–104.

    CAS  Google Scholar 

  • Wang, Y., Gao, Y., Li, C., Gao, H., Zhang, C.C., and Xu, X. (2018). Three substrains of the cyanobacterium Anabaena sp. strain PCC 7120 display divergence in genomic sequences and hetC function. J Bacteriol 200, e00076–18.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Wong, F.C.Y., and Meeks, J.C. (2001). The hetF gene product is essential to heterocyst differentiation and affects HetR function in the cyanobacterium Nostoc punctiforme. J Bacteriol 183, 2654–2661.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Xing, W.Y., Liu, J., Wang, Z.Q., Zhang, J.Y., Zeng, X., Yang, Y., and Zhang, C.C. (2021). HetF protein is a new divisome component in a filamentous and developmental cyanobacterium. mBio 12, e0138221.

    PubMed  Google Scholar 

  • Xing, W.Y., Liu, J., Zhang, J.Y., Zeng, X., and Zhang, C.C. (2022). A proteolytic pathway coordinates cell division and heterocyst differentiation in the cyanobacterium Anabaena sp. PCC 7120. Proc Natl Acad Sci USA 119, e2207963119.

    PubMed  CAS  Google Scholar 

  • Xu, X., Rachedi, R., Foglino, M., Talla, E., and Latifi, A. (2022). Interaction network among factors involved in heterocyst-patterning in cyanobacteria. Mol Genet Genomics 297, 999–1015.

    PubMed  CAS  Google Scholar 

  • Yin, L. (2022). Mechanism study on the coupling of cell division and cell differentiation in heterocyst pattern formation of cyanobacterium Nostoc sp. PCC 7120 (in Chinese). Dissertation for Doctoral Degree. Beijing: Peking University.

    Google Scholar 

  • Yoon, H.S., and Golden, J.W. (1998). Heterocyst pattern formation controlled by a diffusible peptide. Science 282, 935–938.

    PubMed  CAS  Google Scholar 

  • Zeng, X., and Zhang, C.C. (2022). The making of a heterocyst in cyanobacteria. Annu Rev Microbiol 76, 597–618.

    PubMed  CAS  Google Scholar 

  • Zhang, W., Du, Y., Khudyakov, I., Fan, Q., Gao, H., Ning, D., Wolk, C.P., and Xu, X. (2007). A gene cluster that regulates both heterocyst differentiation and pattern formation in Anabaena sp. strain PCC 7120. Mol Microbiol 66, 1429–1443.

    PubMed  CAS  Google Scholar 

  • Zhao, C., Li, Z., Li, T., Zhang, Y., Bryant, D.A., and Zhao, J. (2015). High-yield production of extracellular type-I cellulose by the cyanobacterium Synechococcus sp. PCC 7002. Cell Discov 1, 15004.

    PubMed  CAS  Google Scholar 

  • Zheng, L., Li, Y., Li, X., Zhong, Q., Li, N., Zhang, K., Zhang, Y., Chu, H., Ma, C., Li, G., et al. (2019). Structural and functional insights into the tetrameric photosystem I from heterocyst-forming cyanobacteria. Nat Plants 5, 1087–1097.

    PubMed  CAS  Google Scholar 

  • Zheng, Z., Omairi-Nasser, A., Li, X., Dong, C., Lin, Y., Haselkorn, R., and Zhao, J. (2017). An amidase is required for proper intercellular communication in the filamentous cyanobacterium Anabaena sp. PCC 7120. Proc Natl Acad Sci USA 114, E1405–E1412.

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (32070203), the National Key Research and Development Program of China (2017YFA0503703), National Key Research and Development Program of China (2019YFA0904700, 2021YFA0910700, 2021YFA0909700), and Qidong-SLS Innovation Fund (202001539). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. We would like thank Hong-Xia Lv for technical assistance in time-lapse recording; W. Shen for assistance in protein sequencing; Dr. Ying-Chun Hu, Peng-Yuan Dong, Yun-Chao Xie for their professional assistance in EM sample preparation at the Core Facilities of School of Life Sciences, Peking University; Dr. Dong Liu, Dr. Qi Zhang, Xin-dan Qiu for assistance with MS and Dr. Gui-Lan Li for help with protein purification at the National Center for Protein Sciences at Peking University.

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Correspondence to Yixuan Liu or Jindong Zhao.

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PatU3 plays a central role in coordinating cell division and differentiation in pattern formation of filamentous cyanobacterium Nostoc sp. PCC 7120

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Yin, L., Zheng, Z., Li, Y. et al. PatU3 plays a central role in coordinating cell division and differentiation in pattern formation of filamentous cyanobacterium Nostoc sp. PCC 7120. Sci. China Life Sci. 66, 2896–2909 (2023). https://doi.org/10.1007/s11427-023-2380-1

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