Global Regulation in Cyanobacteria:

      We have spent a number of years elucidating the ways in which cyanobacteria respond to nutrient limitation.  When photosynthetic microbes are starved for a specific nutrient they synthesize systems that help them better scavenge the limiting nutrient.  For example, when cyanobacteria are limited for sulfur they increase their ability to scavenge sulfur by elevating the synthesis of a sulfate transporter, and they also extend the range of sulfur containing molecules that they can use as a sulfur source (Green and Grossman, 1988; Green, Laudenbach and Grossman, 1989; Laudenbach and Grossman, 1991). Some of the most dramatic changes that occur during the starvation of cyanobacteria are termed the ‘general responses’; these responses occur during starvation for any of a number of different nutrients (starvation for nitrogen and sulfur are most commonly used).  These responses include the degradation of the light harvesting complex (the phycobilisome, abbreviated PBS) and the shut-down (and degradation) of photosystem II (Collier and Grossman, 1992; Collier and Grossman, 1994; Collier, Herbert, Fork and Grossman, 1994).

      To elucidate how the general responses to nutrient deprivation are controlled, we have developed a mutant screen using the cyanobacterium Synechococcus sp. Strain PCC7942. The PBS gives cyanobacterial cells their typical blue-green color. When Synechococcus is starved for nitrogen or sulfur it degrades its PBS, which causes the cells to look yellow or bleached (often called chlorosis); this is depicted in Figure 1. Mutants that fail to degrade the PBS remain blue green and can easily be identified by visual inspection of colonies of mutagenized cells grown on solid medium limiting for either sulfur or nitrogen. We have isolated several mutants that are unable to degrade their PBS during nutrient limitation and have identified genes that complement these mutant strains. One of these mutants has a lesion in a gene encoding a small polypeptide, designated NblA, that has homology to putative polypeptides in other cyanobacteria and red algae (Collier and Grossman, 1994).  No catalytic function for this polypeptide has yet been established, although it may turnover along with the PBS polypeptides.  It is possible that NblA tags the PBS for degradation (perhaps in a manner similar to that of ubiquitin). A second mutant was complemented by a gene designated nblB, which encodes a polypeptide with homology to the family of polypeptides involved in attaching chromophores to apophycobiliprotein a subunits (Dolganov and Grossman, 1999).  This protein may be required for removing bilin chromophores from phycobiliprotein subunits prior to their degradation (the removal would be absolutely required for degradation).  A third nonbleaching mutant was complemented by the nblR gene (Schwarz and Grossman, 1998).  NblR is a response regulator that appears to control at least some of the general responses observed during any of a number of different stress conditions. It is required for degradation of PBS and also appears to be necessary for controlling photosynthetic activity during both nutrient limitation and high light conditions; this control is critical for allowing the cells to survive adverse environmental conditions.  NblR appears to be controlled by NblS, a sensor histidine kinase that has a PAS domain (van Waasbergen et al., 2002).  Preliminary results suggest that this PAS domain binds a redox-sensing prosthetic group such as a flavin.  While the signals that control nutrient stress and high light responses have not been clearly established, current data suggests the involvement of either the redox state or the level of active oxygen molecules in the cell.  A diagram depicting the control of nutrient stress and high light responses by the NblS-NblR system is shown in Figure 2. Furthermore, the potential evolution of redox sensors/blue light photoreceptors from redox active electron carriers is depicted in Figure 3.

      We have also been using classical genetics and microarray analyses to explore the role of the NblS homologue (designated DspA) in Synechocystis sp. Strain PCC6803 (Hsiao et al., 2003; Tu et al. 2003).

Figure 1. Cells grown on nutrient replete solid agar (+S) and on agar depleted of sulfur (-S). Note how strongly the cells bleach, although they can survive this condition for an extended period of time.

Figure 2. The complex regulatory network controlling high light and nutrient deprivation conditions.

Figure 3. Potential evolution of blue light photoreceptor and redox controller from redox carrier.

References

Collier J., S. Herbert, D. Fork and A. Grossman (1994) Alterations in photosynthetic electron transport activity in response to nutrient limited growth. Photosyn Res 42:173-183.

Collier, J. L. and A.R. Grossman. (1992) Chlorosis induced by nutrient deprivation in Synechococcus sp. strain PCC 7942: Not all bleaching is the same. J Bacteriol 174:4718-4726.

Collier, J., and A.R. Grossman. (1994) A small peptide elicites the degradation of phycobilisomes during nutrient-limited growth of cyanobacteria. EMBO J 13:1039-1047.

Dolganov, N. and A. R. Grossman (1999) A polypeptide with similarity to phycocyanin a subunit phycocyanobilin lyase involved in degradation of phycobilisomes. J Bacteriol 181:610-617.

Green, L., D. Laudenbach and A.R. Grossman. 1989. A region of the cyanobacterial genome required for sulfate transport. Proc Natl Acad Sci USA  86: 1949-1953.

Green, L.S. and A.R. Grossman.  1988.  Changes in sulfate transport characteristics and protein composition of Anacystis nidulans R2 during sulfate deprivation.  J Bacteriol 170: 583-587.

Hsiao, H.-Y. He, Q., vanWaasbergen, L.G. and A.R. Grossman (2003) Control of photosynthetic and high light-responsive genes by the histidine kinase DspA: Negative and positive regulation and interactions between signal transduction pathways. J Bacteriol. In Press.

Laudenbach, D.E., D. Ehrhardt, L. Green, and A.R. Grossman (1991) The isolation and characterization of a sulfur-regulated gene encoding a periplasmic localized protein with sequence similarity to rhodanese. J Bacteriol 173:2751-2760.

Schwarz, R. and A. R. Grossman (1998) A response regulator of cyanobacteria integrates diverse environmental signals and is critical for survival under extreme conditions. Proc Natl Acad Sci USA 95:11008-11013.

Tu, C.-J., Shrager, J., Burnap, R. L., Postier, B. L. and A. R. Grossman (2003) The Consequences of a deletion in dspA on transcript accumulation in Synechocystis sp. Strain PCC6803. J Bacteriol. In Press.

Van Waasbergen, L., N. Dolganov and A. R. Grossman (2002) nblS, a gene involved in controlling photosynthesis-related gene expression during high light and nutrient stress in  Synechococcus elongatus PCC 7942. J Bacteriol 184:2481-90.