HETEROCYST - Cyanobacteria - page 223

with the inactive inhibitor present in adjacent vegetative cells and activate it so that the adjacent
cells are inhibited.
The controversy with regard to the chemical nature of the inhibitor(s) seems to have been set at
rest with the discovery of a number of genes and the interaction of their products. The discovery of
hetR (Buikema and Haselkorn, 1991b), patA (Liang et al ., 1992), patB (Liang et al ., 1993), patS (Yoon
and Golden, 1998), hetN (Ernst et al ., 1992) and hetC (Xu and Wolk, 2001) have heralded a new phase
in understanding pattern formation. The pattern suppression gene, patS that encodes a polypeptide
of 15-17 amino acids with a C-terminal pentapeptide (RGSGR) sequence is responsible for pattern
formation and synthetic RGSGR sequence at 1 µM inhibits the formation of heterocysts (Yoon and
Golden, 1998). PatS, synthesized in the mature heterocysts, is the main inhibitor that is supposed
to form the gradient in the vegetative cells. Yoon and Golden (2001) elegantly demonstrated this by
making transcriptional fusions between P patS - gfp and showed that at the time the products of asymmetric
cell division are to be resolved for proheterocyst differentiation it is the level of PatS that deterimes
the course of events. Thus PatS controls the pattern of intercalary heterocysts. Like PatS, HetN (a
gene product of hetN , Ernst et al ., 1992) is another negative regulator of heterocyst differentiation.
PatS and HetN act independently and have complementary functions and help in the establishment
and maintenance of the pattern. Complete inactivation of both patS and hetN leads to an aberrant
multiple-chain heterocyst phenotype (Borthakur et al ., 2005). A patA null mutant formed terminal
heterocysts only (Orozoco et al ., 2006) and a mutation in patB caused a delay in heterocyst formation.
HetC regulates a number of cell division genes (Xu and Wolk, 2001).
HetR is the master regulator of heterocyst differentiation and its up-regulation is very important
for heterocyst differentiation to be initiated. That is HetR protein activates its own transcription
and patS gene expression. PatS inhibits the upregulation of hetR by preventing the DNA-binding
activity of HetR (Black et al ., 1993; Golden and Yoon, 2003; Huang et al ., 2004). Signalling between
HetR, PatS and HetN is important for normal pattern formation and maintenance but when it is
lost it leads to loss of heterocyst differentiation (Khudyakov and Golden, 2004). To explain the role
of HetR, PatS and HetN in pattern formation of heterocysts four models have been presented. The
fi rst one proposed by Allard et al . (2007) visualized pattern formation without patterning proteins,
HetR, PatS and HetN. These workers laid emphasis on cell growth and division together with the
dynamics of fi xed nitrogen. Three important testable hypotheses put forward by them are (i) the
initial heterocyst positions can be correlated to the fast growing and or small vegetative cells; (ii)
the release of fi xed nitrogen albeit at small rates 10% or so will trigger PatS-induced resolution of
proheterocysts and (iii) fi xed nitrogen effl ux pumps operating in vegetative cells cause the gradients
in fi xed nitrogen and leads to the resolution of proheterocysts. The rest of the three models are on
similar lines. Risser and Callahan (2009) envisaged an activator-inhibitor model. HetR is the activator
that forms gradients in the vegetative cells adjacent to the heterocysts and PatS and HetN are the two
inhibitors originating from heterocysts also form gradients in vegetative cells. One of the inhibitors
is overexpressed leading to activator decay committing the cell to differentiate into a proheterocyst.
Gerdtzen et al . (2009) not only took into account the gene interactions between ntcA , hetR and patS
involved in heterocyst differentiation but also the infl uence of knock-out or overexpression of the
individual elements. Primarily based on the one-dimensional activator-inhibition model, this model
highlighted the role of HetR as an activator and PatS as the inhibitor that can inhibit the production of
HetR (Figs. 5 and 6). The model presented by Zhu et al . (2010) is a mathematical model incorporating
the molecular interactions that regulate heterocyst pattern formation and maintenance in Anabaena
sp. strain PCC 7120. This model is based on the concept of a non-diffusing activator (HetR) and two
inhibitors (PatS and HetN) that show different diffusion rates and temporal expression patterns.