Control of cell division in Streptococcus pneumoniae by the conserved Ser/Thr protein kinase StkP

ABSTRACTHow bacteria control proper septum placement at midcell, to guarantee the generation of identical daughter cells, is still largely unknown. Although different systems involved in the selection of the division site have been described in selected species, these do not appear to be widely conserved. Here, we report that LocZ (Spr0334), a newly identified cell division protein, is involved in proper septum placement inStreptococcus pneumoniae. We show thatlocZis not essential but that its deletion results in cell division defects and shape deformation, causing cells to divide asymmetrically and generate unequally sized, occasionally anucleated, daughter cells. LocZ has a unique localization profile. It arrives early at midcell, before FtsZ and FtsA, and leaves the septum early, apparently moving along with the equatorial rings that mark the future division sites. Consistently, cells lacking LocZ also show misplacement of the Z-ring, suggesting that it could act as a positive regulator to determine septum placement. LocZ was identified as a substrate of the Ser/Thr protein kinase StkP, which regulates cell division in S. pneumoniae. Interestingly, homologues of LocZ are found only in streptococci, lactococci, and enterococci, indicating that this close phylogenetically related group of bacteria evolved a specific solution to spatially regulate cell division.IMPORTANCEBacterial cell division is a highly ordered process regulated in time and space. Recently, we reported that the Ser/Thr protein kinase StkP regulates cell division in Streptococcus pneumoniae, through phosphorylation of several key proteins. Here, we characterized one of the StkP substrates, Spr0334, which we named LocZ. We show that LocZ is a new cell division protein important for proper septum placement and likely functions as a marker of the cell division site. Consistently, LocZ supports proper Z-ring positioning at midcell. LocZ is conserved only among streptococci, lactococci, and enterococci, which lack homologues of the Min and nucleoid occlusion effectors, indicating that these bacteria adapted a unique mechanism to find their middle, reflecting their specific shape and symmetry.

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Identification of Multiple Substrates of the StkP Ser/Thr Protein Kinase in Streptococcus pneumoniae

Journal of Bacteriology ◽

10.1128/jb.01564-09 ◽

2010 ◽

Vol 192 (14) ◽

pp. 3629-3638 ◽

Cited By ~ 49

Author(s):

Linda Nováková ◽

Silvia Bezoušková ◽

Petr Pompach ◽

Petra Špidlová ◽

Lenka Sasková ◽

...

Keyword(s):

Cell Division ◽

Streptococcus Pneumoniae ◽

Protein Kinase ◽

Intracellular Signaling ◽

Regulation Of Gene Expression ◽

Dependent Manner ◽

Α Subunit ◽

Component Systems ◽

Two Component ◽

Two Component Systems

ABSTRACT Monitoring the external environment and responding to its changes are essential for the survival of all living organisms. The transmission of extracellular signals in prokaryotes is mediated mainly by two-component systems. In addition, genomic analyses have revealed that many bacteria contain eukaryotic-type Ser/Thr protein kinases. The human pathogen Streptococcus pneumoniae encodes 13 two-component systems and has a single copy of a eukaryotic-like Ser/Thr protein kinase gene designated stkP. Previous studies demonstrated the pleiotropic role of the transmembrane protein kinase StkP in pneumococcal physiology. StkP regulates virulence, competence, and stress resistance and plays a role in the regulation of gene expression. To determine the intracellular signaling pathways controlled by StkP, we used a proteomic approach for identification of its substrates. We detected six proteins phosphorylated on threonine by StkP continuously during growth. We identified three new substrates of StkP: the Mn-dependent inorganic pyrophosphatase PpaC, the hypothetical protein spr0334, and the cell division protein DivIVA. Contrary to the results of a previous study, we did not confirm that the α-subunit of RNA polymerase is a target of StkP. We showed that StkP activation and substrate recognition depend on the presence of a peptidoglycan-binding domain comprising four extracellular penicillin-binding protein- and Ser/Thr kinase-associated domain (PASTA domain) repeats. We found that StkP is regulated in a growth-dependent manner and likely senses intracellular peptidoglycan subunits present in the cell division septa. In addition, stkP inactivation results in cell division defects. Thus, the data presented here suggest that StkP plays an important role in the regulation of cell division in pneumococcus.

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Cell division protein kinase 5

Targeted Protein Database ◽

10.2970/tpdb.2009.264 ◽

2009 ◽

Author(s):

Amy Fu

Keyword(s):

Cell Division ◽

Protein Kinase ◽

Cell Division Protein

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Faculty Opinions recommendation of Cell division in cocci: localization and properties of the Streptococcus pneumoniae FtsA protein.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1023513.274662 ◽

2005 ◽

Author(s):

William Margolin

Keyword(s):

Cell Division ◽

Streptococcus Pneumoniae

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Faculty Opinions recommendation of PASTA repeats of the protein kinase StkP interconnect cell constriction and separation of Streptococcus pneumoniae.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732228630.793540822 ◽

2017 ◽

Author(s):

Alain Filloux

Keyword(s):

Streptococcus Pneumoniae ◽

Protein Kinase

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Protein kinase cascades in meiotic and mitotic cell cycle control

Biochemistry and Cell Biology ◽

10.1139/o90-194 ◽

1990 ◽

Vol 68 (12) ◽

pp. 1297-1330 ◽

Cited By ~ 81

Author(s):

Steven L. Pelech ◽

Jasbinder S. Sanghera ◽

Maleki Daya-Makin

Keyword(s):

Cell Cycle ◽

Cell Division ◽

Protein Kinase ◽

Tyrosine Kinases ◽

Somatic Cells ◽

Protein Tyrosine Kinases ◽

Sea Star ◽

Protein Tyrosine ◽

Threonine Kinases ◽

Cell Division Control

Eukaryotic cell cycle progression during meiosis and mitosis is extensively regulated by reversible protein phosphorylation. Many cell surface receptors for mitogens are ligand-stimulated protein-tyrosine kinases that control the activation of a network of cytoplasmic and nuclear protein-serine(threonine) kinases. Over 30 plasma membrane associated protein-tyrosine kinases are encoded by proto-oncogenes, i.e., genes that have the potential to facilitate cancer when disregulated. Proteins such as ribosomal protein S6, microtubule-associated protein-2, myelin basic protein, and casein have been used to detect intracellular protein-serine(threonine) kinases that are activated further downstream in growth factor signalling transduction cascades. Genetic analysis of yeast cell division control (cdc) mutants has revealed another 20 or so protein-serine(threonine) kinases. One of these, specified by the cdc-2 gene in Schizosaccharomyces pombe, has homologs that are stimulated during M phase in maturing sea star and frog oocytes and mammalian somatic cells. Furthermore, during meiotic maturation in these echinoderm and amphibian oocytes, this is followed by activation of many of the same protein-serine(threonine) kinases that are stimulated when quiescent mammalian somatic cells are prompted with mitogens to traverse from G0 to G1 phase. These findings imply that a similar protein kinase cascade may oversee progression at multiple points in the cell cycle.Key words: protein kinases, mitosis, meiosis, oncogenes, cell division control.

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