User talk:NamitHolay

Sporulation is a process generally occurring in Gram positive bacteria like Bacillus and Clostridium in which the bacterial cell transforms into a dormant, tough and non-reproducible spore in order to survive unfavorable conditions.

In B.subtilis, sporulation is triggered by a limitation of nutrients in the surrounding environment. It is brought about by a phosphorelay system. This system is a complex variant of the common prokaryotic signal transduction machinery, the two-component regulatory system (TCS). Phosphorelays are also present in eukaryotes but with certain modifications.

The Phosphorelay System
Phosphorelays are a complex version of the TCS, where a membrane sensor kinase transfers the phosphoryl group to a response regulator(RR), which has a domain with the conserved aspartate residue but lacks the output domain. The RR then transfers this phosphoryl group to a histidine containing phosphotransfer protein (HPt). HPt functions as the phosphodonor for the terminal response regulator which has the output domain controlling a cellular response.

Mechanism of Sporulation in B.Subtilis
Sporulation in Bacillus subtilis is regulated via a phosphorelay system in which five different sensor kinases- KinA, KinB, KinC, KinD and KinE- zct as phosphoryl donors for the single domain response regulator Spo0F. Spo0F then transfers the phosphoryl group to the histidine-containing phosphotransfer protein(HPt) Spo0B, which then transfers it to the DNA-binding response regulator Spo0A, a protein which controls the expression of several downstream genes, including those regulating sporulation.

The signal causing the autophosphorylation of KinA is not known.

Regulation
Since sporulation is an energy-consuming process and becomes irreversible at an early stage it is tightly regulated and coordinated with other physiological functions, conditions and environmental factors like availability of nutrients, competence, DNA impairment etc.

Nutrient Availability
Availability of nutrients in the environment plays a crucial role in regulating the sporulation cascade in B. subtilis. Availability of sugars and in conditions which support vegetative growth, different genes like kipl, rapB, spo0E, yisl and ynzD are expressed and these inhibit the cascade by dephosphorylating various components of it. Kipl inhibits the cascade by blocking the auto phosphorylation of the sensor kinase KinA, while RapB, Spo0E, Yisl and YnzD are phosphatases that inhibit the cascade by dephosphorylating Spo0F-P (RapB) and Spo0A-P (Spo0E, Yisl and YnzD).

DNA Impairment
Sporulation does not take place if the genes required for sporulation are impaired. It has been hypothesized that when DNA replication is affected, change in levels of a replication initiation factor DnaA are seen. This in turn regulates sda gene which when overexpressed leads to inhibition of phosphorylation of KinA. Hence the Sda mediated regulation prevents B.Subtilis from entering into sporulation if the genes required for completion of the process are impaired.

Competence
Genetic competence is a complex phenotypic state that is triggered in B.subtilis during the late exponential/early stationary phase. Though competence is a stress response to hostile environmental conditions, sporulation and competence are mutually exclusive events and are reciprocally regulated. Induction of competence activates rapA and rapE genes and the subsequent proteins RapA and RapE trigger the dephosphorylation of Spo0F-P, thereby inhibiting sporulation. RapA and RapE mediated control is also attained by pentapeptide inhibitors PhrA and PhrE which inhibit the phosphatase activity of the former proteins. The phrE gene is activated by Spo0E (σH), an alternative sigma factor expressed during the growth phase transition. σH not only block the sporulation cascade but also enhances development of competence in B.subtilis. The response regulator in competence is a protein called ComA and is prevented from binding to DNA by RapC, RapF and RapH proteins. σH activates the expression of PhrC and PhrF which inhibit the RapC and RapF proteins from binding to ComA(9,16).

Prokaryotic vs. Eukaryotic phosphorelays
Phosphorelay systems are a minority of TCS family in prokaryotes but are a major component in eukaryotes TCSs. However phosphorelay systems have not been found yet in animals. Moreover the phosphorelay systems found in lower eukaryotes and plants are predominantly located in the cytosol in contrast to prokaryotic membrane bound system with the exception of a few like Sln1 of yeast, Tcsb of A.nidulans etc. Also the hybrid kinases found in eukaryotic systems donot have a HPt domain unlike most of prokaryotes.