Cyanobacterial Heterocysts

Abstract

Cyanobacteria are phototrophic bacteria carrying out oxygen‐producing photosynthesis. Indeed, cyanobacteria were the inventors of oxygenic photosynthesis carried out by eukaryotic algae and plants. Besides showing the capability of building their cellular carbon from carbon dioxide, available in the atmosphere, several strains of cyanobacteria have also acquired the ability to fix molecular dinitrogen (N2). As the enzyme responsible for nitrogen fixation (nitrogenase) is highly sensitive towards oxygen, nitrogen fixation and oxygenic photosynthesis cannot take place simultaneously in cyanobacterial cells. To solve this problem, some filamentous strains are able to restrict N2 fixation to a special cell type, the heterocyst. Heterocysts are specialised, morphologically distinct, terminally differentiated cells that develop, in the absence of alternative sources of combined nitrogen, mostly in a semiregular pattern along the filament. Thus, a filament containing heterocysts provides division of labour between photosynthetic carbon dioxide fixation (in vegetative cells) and anaerobic N2 fixation (in heterocysts). These cyanobacteria represent true multicellular organisms with profound morphological cell differentiation and sophisticated intercellular communication systems.

Key Concepts:

  • Although bacteria, some filamentous cyanobacteria are true multicellular organisms, showing different cell types for specialised tasks.

  • When starved for a source of combined nitrogen these cyanobacteria start a programme of cell differentiation resulting in a pattern of semiregularly spaced heterocysts along the filament.

  • Heterocysts develop from vegetative cells, the sites for oxygenic photosynthesis, and provide a microoxic environment for the oxygen‐labile nitrogenase.

  • Nitrogenase is the enzyme responsible for N2 fixation and allows the organism to live from sunlight, air (carbon dioxide and N2) and some minerals.

  • Under nitrogen fixing conditions the two cell types rely on each other and exchange metabolites and signalling molecules, presumably via protein‐complex‐mediated cell‐to‐cell contact or the continuous periplasmic space that surrounds all cells of the multicellular filament.

  • Global nitrogen control factor NtcA controls activation of many genes involved in heterocyst differentiation and function.

  • HetR, the activator of heterocyst differentiation, is regulated by NtcA, known inhibitors of heterocyst differentiation PatS and HetN, as well as by proteins HetF and PatA controlling HetR turnover.

  • The pattern of spaced heterocysts is regulated by inhibitor gradients that promote the decay of HetR, confirming mathematical models of two‐dimensional pattern formation in heterocystous cyanobacteria.

Keywords: cyanobacteria; differentiation; nitrogen fixation; pattern formation; cell communication

Figure 1.

Ultrastructure of Anabaena strain PCC 7120. The structures of a terminal heterocyst and two vegetative cells visualised by transmission electron microscopy.

Figure 2.

Intracellular solute exchange could occur via a periplasmic route or with the aid of cell‐to‐cell connections in a filament of Anabaena. (a) Electron micrograph of the septum between two vegetative cells of an Anabaena filament. Purple arrows point to electron dense material traversing the septum through the periplasmic space that could present putative cell‐to‐cell bridges. (b) Filament of Anabaena sp. PCC 7120 (strain CSAM137; Flores et al., ) expressing an SepJ‐GFP fusion protein. GFP is found in the middle of the septum between two cells. Courtesy of Vicente Mariscal, CSIC and Universidad de Sevilla, Spain. (c) Scheme of intracellular and periplasmatic routes of solutes between the cells of a heterocystous filament: Barrels represent exporter, as putative sugar transporters of vegetative cells, tetrads represent importers of solutes, as amino acids imported by heterocysts. Protein complexes are localised in the septum, putatively composed of SepJ and Fra proteins that allow the transport of small solutes (small yellow dots) between adjacent cells of the filaments. Half circles and half squares represent binding proteins and dots represent solutes that diffuse through the periplasmic space. Artwork of (c) by Ingeborg Schleip is gratefully acknowledged.

Figure 3.

Fluxes of carbon, nitrogen and reductant in heterocysts. Heterocysts act as a sink for carbohydrates (sucrose?) from vegetative cells and as a source of fixed nitrogen (glutamine, NH4+, aspartate?) to vegetative cells. Solid lines represent fluxes of carbon and nitrogen; dashed lines refer to fluxes of reducing equivalents; question marks indicate uncertainties. Enzymes, enzyme complexes and components of the electron transport chains are circled; storage compounds are in italic; metabolites are depicted in regular letters. Abbreviations: AcCoA, acetyl‐coenzyme A; arg, arginine; asp, aspartate; b6/f, cytochrome b6/f complex; cit, citrate; fruc, fructose; F6P, fructose 6‐phosphate; Fdx, vegetative cell‐type ferredoxin; FdxH, heterocyst‐specific ferredoxin; FNR, ferredoxin: NADP+ oxidoreductase; G6P, glucose 6‐phosphate; 6PG, 6‐phosphogluconate; gln, glutamine; glu, glutamate; gluc, glucose; H2ase, uptake hydrogenase; isocit, isocitrate; αKG, α‐ketoglutarate; NDH, NAD(P)H dehydrogenase; oaa, oxaloacetate; ox. PPC, oxidative pentose phosphate cycle; P, inorganic phosphate; PEP, phosphoenolpyruvate; PGA, 3‐phosphoglycerate; PSI, photosystem I; pyr, pyruvate; R5P, ribulose 5‐phosphate; RET, respiratory electron transport; trioseP, triose phosphate. Not all intermediates are depicted. Modified from Wolk et al. (, Figure ). Copyright © Kluwer Academic Publishers 1994, with kind permission.

Figure 4.

Increased expression of GFP from the ntcA promoter in (pro)heterocysts 8 h after nitrogen step‐down. The micrograph is an overlay of red (autofluorescence) and green (GFP fluorescence) channels (see also Olmedo‐Verd et al., ).

close

References

Awai K, Lechno‐Yossef S and Wolk CP (2009) Heterocyst envelope glycolipids. In: Wada M (ed.) Lipids in Photosynthesis: Essential and Regulatory Functions, pp. 179–202. Dordrecht: Springer Science+Business Media B.V.

Bauer CC, Buikema WJ, Black K and Haselkorn R (1995) A short‐filament mutant of Anabaena sp. strain PCC 7120 that fragments in nitrogen‐deficient medium. Journal of Bacteriology 177: 1520–1526.

Black K, Buikema WJ and Haselkorn R (1995) The hglK gene is required for localization of heterocyst‐specific glycolipids in the cyanobacterium Anabaena sp. strain PCC 7120. Journal of Bacteriology 177: 6440–6448.

Black TA, Cai Y and Wolk CP (1993) Spatial expression and autoregulation of hetR, a gene involved in the control of heterocyst development in Anabaena. Molecular Microbiology 9: 77–84.

Böhme H (1998) Regulation of nitrogen fixation in heterocyst‐forming cyanobacteria. Trends in Plant Science 3: 346–351.

Buikema WJ and Haselkorn R (1991) Characterization of a gene controlling heterocyst differentiation in the cyanobacterium Anabaena 7120. Genes & Development 5: 321–330.

Cai Y and Wolk CP (1997) Anabaena sp. strain PCC 7120 responds to nitrogen deprivation with a cascade‐like sequence of transcriptional activations. Journal of Bacteriology 179: 267–271.

Campbell EL, Summers ML, Christman H, Martin ME and Meeks JC (2007) Global gene expression patterns of Nostoc punctiforme in steady‐state dinitrogen‐grown heterocyst‐containing cultures and at single time points during the differentiation of akinetes and hormogonia. Journal of Bacteriology 189: 5247–5256.

Cohen MF, Meeks JC, Cai Y and Wolk CP (1998) Transposon mutagenesis of heterocyst‐forming filamentous cyanobacteria. In: McIntosh L (ed.) Photosynthesis: Molecular Biology of Energy Capture. Methods in Enzymology, Vol. 297, pp. 3–17. New York: Academic Press.

Durner J and Böger P (1995) Ubiquitin in the prokaryote Anabaena variabilis. Journal of Biological Chemistry 270: 3720–3725.

Ehira S, Ohmori M and Sato N (2003) Genome‐wide expression analysis of the responses to nitrogen deprivation in the heterocyst‐forming cyanobacterium Anabaena sp. strain PCC 7120. DNA Research 10: 97–113.

Fan Q, Huang G, Lechno‐Yossef S et al. (2005) Clustered genes required for synthesis and deposition of envelope glycolipids in Anabaena sp. strain PCC 7120. Molecular Microbiology 58: 227–243.

Fay P (1992) Oxygen relations of nitrogen fixation in cyanobacteria. Microbiological Reviews 56: 340–373.

Fiedler G, Arnold M, Hannus S and Maldener I (1998) The DevBCA exporter is essential for envelope formation in heterocysts of the cyanobacterium Anabaena sp. strain PCC 7120. Molecular Microbiology 27: 1193–1202.

Flores E, Herrero A, Wolk CP and Maldener I (2006) Is the periplasm continuous in filamentous multicellular cyanobacteria? Trends in Microbiology 14: 439–443.

Flores E, Pernil R, Muro‐Pastor AM et al. (2007) Septum‐localized protein required for filament integrity and diazotrophy in the heterocyst‐forming cyanobacterium Anabaena sp. strain PCC 7120. Journal of Bacteriology 189: 3884–3890.

Forchhammer K (2004) Global carbon/nitrogen control by PII signal transduction in cyanobacteria: from signals to targets. FEMS Microbiological Reviews 28: 319–333.

Gallon JR (1992) Reconciling the incompatible: N2 fixation and O2. New Phytologist 122: 571–609.

Hanson TE, Forchhammer K, Tandeau de Marsac N and Meeks JC (1998) Characterization of the glnB gene product of Nostoc punctiforme strain ATCC 29133: glnB or the PII protein may be essential. Microbiology 144: 1537–1547.

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. Proceedings of the National Academy of Sciences of the USA 101: 4848–4853.

Jang J, Shi L, Tan H, Janicki A and Zhang C‐C (2009) Mutual regulation of ntcA and hetR during heterocyst differentiation requires two similar PP2C‐type protein phosphatases, PrpJ1 and PrpJ2, in Anabaena sp. strain PCC 7120. Journal of Bacteriology 191: 6059–6066.

Jones KM and Haselkorn R (2002) Newly identified cytochrome c oxidase operon in the nitrogen‐fixing cyanobacterium Anabaena sp. strain PCC 7120 specifically induced in heterocysts. Journal of Bacteriology 184: 2491–2499.

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. Proceedings of the National Academy of Sciences of the USA 89: 5655–5659.

Luque I, Flores E and Herrero A (1994) Molecular mechanism for the operation of nitrogen control in cyanobacteria. European Molecular Biology Organisation Journal 15: 2862–2869.

Maldener I, Hannus S and Kammerer M (2003) Description of five mutants of the cyanobacterium Anabaena sp. strain PCC 7120 affected in heterocyst differentiation and identification of the transposon‐tagged genes. FEMS Microbiological Letters 224: 205–213.

Mariscal V, Herrero A and Flores E (2007) Continuous periplasm in a filamentous, heterocyst‐forming cyanobacterium. Molecular Microbiology 65: 1139–1145.

Meinhardt H (1994) Biological pattern formation: new observations provide support for theoretical predictions. BioEssays 16: 627–632.

Merino‐Puerto V, Mariscal V, Mullineaux CW, Herrero A and Flores E (2010) Fra proteins influencing filament integrity, diazotrophy and localization of septal protein SepJ in the heterocyst‐forming cyanobacterium Anabaena sp. Molecular Microbiology 75: 1159–1170.

Moslavac S, Nicolaisen K, Mirus O et al. (2007) A TolC‐like protein is required for heterocyst development in Anabaena sp. strain PCC 7120. Journal of Bacteriology 189: 7887–7895.

Mullineaux CW, Mariscal V, Nenninger A et al. (2008) Mechanism of intercellular molecular exchange in heterocyst‐forming cyanobacteria. European Molecular Biology Organisation Journal 27: 1299–1308.

Muro‐Pastor AM, Valladares A, Flores E and Herrero A (2002) Mutual dependence of the expression of the cell differentiation regulatory protein HetR and the global nitrogen regulator NtcA during heterocyst development. Molecular Microbiology 44: 1377–1385.

Nayar AS, Yamaura H, Rajagopalan R, Risser DD and Callahan SM (2007) FraG is necessary for filament integrity and heterocyst maturation in the cyanobacterium Anabaena sp. strain PCC 7120. Microbiology 153: 601–607.

Nicolaisen K, Hahn A and Schleiff E (2009) The cell wall in heterocyst formation by Anabaena sp. PCC 7120. Journal of Basic Microbiology 49: 5–24.

Olmedo‐Verd E, Muro‐Pastor AM, Flores E and Herrero A (2006) Localized induction of the ntcA regulatory gene in developing heterocysts of Anabaena sp. strain PCC 7120. Journal of Bacteriology 188: 6694–6699.

Olmedo‐Verd E, Valladares A, Flores E, Herrero A and Muro‐Pastor AM (2008) Role of two NtcA‐binding sites in the complex ntcA gene promoter of the heterocyst‐forming cyanobacterium Anabaena sp. strain PCC 7120. Journal of Bacteriology 190: 7584–7590.

Paz‐Yepes J, Flores E and Herrero A (2009) Expression and mutational analysis of the glnB genomic region in the heterocyst‐forming cyanobacterium Anabaena sp. strain PCC 7120. Journal of Bacteriology 191: 2353–2561.

Risser DD and Callahan SM (2008) HetF and PatA control levels of HetR in Anabaena sp. strain PCC 7120. Journal of Bacteriology 190: 7645–7654.

Risser DD and Callahan SM (2009) Genetic and cytological evidence that heterocyst patterning is regulated by inhibitor gradients that promote activator decay. Proceedings of the National Academy of Sciences of the USA 106: 19884–19888.

Shi Y, Zhao W, Zhang W, Ye Z and Zhao J (2006) Regulation of intracellular free calcium concentration during heterocyst differentiation by HetR and NtcA in Anabaena sp. PCC 7120. Proceedings of the National Academy of Sciences of the USA 103: 11334–11339.

Tanigawa R, Shirokane M, Maeda Si S et al. (2002) Transcriptional activation of NtcA‐dependent promoters of Synechococcus sp. PCC 7942 by 2‐oxoglutarate in vitro. Proceedings of the National Academy of Sciences of the USA 99: 4251–4255.

Thiel T, Lyons EM, Erker JC and Ernst A (1995) A second nitrogenase in vegetative cells of a heterocyst‐forming cyanobacterium. Proceedings of the National Academy of Sciences of the USA 92: 9358–9362.

Valladares A, Flores E and Herrero A (2008) Transcription activation by NtcA and 2‐oxoglutarate of three genes involved in heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120. Journal of Bacteriology 190: 6126–6133.

Valladares A, Herrero A, Pils D, Schmetterer G and Flores E (2003) Cytochrome c oxidase genes required for nitrogenase activity and diazotrophic growth in Anabaena sp. PCC 7120. Molecular Microbiology 47: 1239–1249.

Valladares A, Muro‐Pastor AM, Herrero A and Flores E (2004) The NtcA‐dependent P1 promoter is utilized for glnA expression in N2‐fixing heterocysts of Anabaena sp. strain PCC 7120. Journal of Bacteriology 186: 7337–7343.

Vázquez‐Bermúdez MF, Herrero A and Flores E (2003) Carbon supply and 2‐oxoglutarate effects on expression of nitrate reductase and nitrogen‐regulated genes in Synechococcus sp. strain PCC 7942. FEMS Microbiological Letters 221: 155–159.

Walsby AE (1985) The permeability of heterocysts to the gases nitrogen and oxygen. Proceedings of the Royal Society of London B 226: 345–366.

Wang L, Sun YP, Chen WL, Li JH and Zhang C‐C (2002) Genomic analysis of protein kinases, protein phosphatases and two‐component regulatory systems of the cyanobacterium Anabaena sp. strain PCC 7120. FEMS Microbiological Letters 217: 155–165.

Wolk P, Ernst A and Elhai J (1994) Heterocyst metabolism and development. In: Bryant DA (ed.) The Molecular Biology of Cyanobacteria, pp. 769–823. Dordrecht: Kluwer Academic Publishers.

Yoon HS and Golden JW (1998) Heterocyst pattern formation controlled by a diffusible peptide. Science 282: 935–938.

Zhang C‐C, Gonzalez L and Phalip V (1998) Survey, analysis and genetic organization of genes encoding eukaryotic‐like signaling proteins in a cyanobacterial genome. Nucleic Acids Research 26: 3619–3625.

Zhang Y, Pu H, Wang Q et al. (2007) PII is important in regulation of nitrogen metabolism but not required for heterocyst formation in the cyanobacterium Anabaena sp. PCC 7120. Journal of Biological Chemistry 282: 33641–33648.

Zhou R, Wei X, Jiang N et al. (1998) Evidence that HetR protein is an unusual serine‐type protease. Proceedings of the National Academy of Sciences of the USA 95: 4959–4963.

Zhou R and Wolk CP (2003) A two‐component system mediates developmental regulation of biosynthesis of a heterocyst polysaccharide. Journal of Biological Chemistry 278: 19939–19946.

Further Reading

Flores E and Herrero A (2010) Compartmentalized function through cell differentiation in filamentous cyanobacteria. Nature Reviews. Microbiology 8: 39–50.

Kumar K, Mella‐Herrera RA and Golden JW (2010) Cyanobacterial Heterocysts. Cold Spring Harbor Perspectives in Biology 2009 2: a000315, originally published online February 24, 2010, pp. 1–19.

Xu X, Elhai J and Wolk CP (2008) Transcriptional and developmental responses by Anabaena to deprivation of fixed nitrogen. In: Herrero A and Flores E (eds) The Cyanobacteria. Molecular Biology, Genomics and Evolution. Norfolk, UK: Caister Academic Press.

Zhang C‐C, Laurent S, Sakr S, Peng L and Bédu S (2006) Heterocyst differentiation and pattern formation in cyanobacteria: a chorus of signals. Molecular Microbiology 59: 367–375.

Zhao J and Wolk CP (2008) Developmental biology of heterocysts, 2006. In: Whitworth DE (ed.) Myxobacteria: Multicellularity and Differentiation, pp. 397–418. Washington, DC: ASM Press.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Maldener, Iris, and Muro‐Pastor, Alicia M(Oct 2010) Cyanobacterial Heterocysts. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000306.pub2]