<i>Myxococcus</i> CsgA, <i>Drosophila</i> Sniffer, and human HSD10 are cardiolipin phospholipases

Boynton, Tye O.; Shimkets, Lawrence J.

doi:10.1101/gad.268482.115

Cited by 46 publications

(53 citation statements)

References 67 publications

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“…For example, the atypical receiver domain of Streptomyces venezuelae JadR1 is bound by jadomycin B, causing JadR1 to dissociate from DNA, and the acylated antibiotic undecylprodigiosin of Streptomyces coelicolor may use a similar mechanism to modulate DNA‐binding activity of the atypical response regulator RedZ (Wang et al , ). Conceivably, FruA activity could likewise be regulated by binding of M. xanthus diacylglycerols, which have been implicated in C‐signaling (Boynton and Shimkets, ). Alternatively, FruA could be regulated by a posttranslational modification other than phosphorylation or by binding to another protein (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…One theory states that the C‐signal is a 17‐kDa fragment of CsgA produced by the specific proteolytic activity of PopC at the cell surface (Kim and Kaiser, ; Lobedanz and Sogaard‐Andersen, ; Rolbetzki et al , ). The other theory is that diacylglycerols released from the inner membrane by cardiolipin phospholipase activity of intact CsgA are the C‐signal (Boynton and Shimkets, ). However, in neither case has the signal receptor been identified, so our understanding of C‐signaling is incomplete.…”

Section: Introductionmentioning

confidence: 99%

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Systematic analysis of the Myxococcus xanthus developmental gene regulatory network supports posttranslational regulation of FruA by C‐signaling

Saha

Patra

Igoshin

et al. 2019

Molecular Microbiology

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Upon starvation Myxococcus xanthus undergoes multicellular development. Rod-shaped cells move into mounds in which some cells differentiate into spores. Cells begin committing to sporulation at 24-30 h poststarvation, but the mechanisms governing commitment are unknown. FruA and MrpC are transcription factors that are necessary for commitment. They bind cooperatively to promoter regions and activate developmental gene transcription, including that of the dev operon. Leading up to and during the commitment period, dev mRNA increased in wild type, but not in a mutant defective in C-signaling, a short-range signaling interaction between cells that is also necessary for commitment. The C-signaling mutant exhibited ~20-fold less dev mRNA than wild type at 30 h poststarvation, despite a similar level of MrpC and only 2-fold less FruA. Boosting the FruA level twofold in the C-signaling mutant had little effect on the dev mRNA level, and dev mRNA was not less stable in the C-signaling mutant. Neither did high cooperativity of MrpC and FruA binding upstream of the dev promoter explain the data. Rather, our systematic experimental and computational analyses support a model in which C-signaling activates FruA at least ninefold posttranslationally in order to commit a cell to spore formation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systematic analysis of the Myxococcus xanthus developmental gene regulatory network supports posttranslational regulation of FruA by C‐signaling

Saha

Patra

Igoshin

et al. 2019

Molecular Microbiology

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“…An alternate model is that cardiolipin phospholipase activity of intact CsgA releases diacylglycerols from the inner membrane that are C-signal [94] (Figure I, bottom pathway). This model is supported by analysis of a csgA suppressor mutation that causes overexpression of socA [95], which codes for a cardiolipin phospholipase [94], by mutational analysis of csgA [96], and by developmental rescue of a csgA socA mutant by a lipid fraction enriched in diacylglycerols from Myxococcus [94]. The two models for the identity of C-signal are not mutually exclusive.…”

Section: Overview Of the Grn Governing Myxococcus Developmentmentioning

confidence: 99%

Highly Signal-Responsive Gene Regulatory Network Governing Myxococcus Development

Kroos

2017

Trends in Genetics

106

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The bacterium Myxococcus xanthus undergoes multicellular development when starved. Thousands of cells build mounds in which some differentiate into spores. This remarkable feat and the genetic tractability of Myxococcus provide a unique opportunity to understand evolution of gene regulatory networks (GRNs). Recent work has revealed a GRN involving interconnected cascades of signal-responsive transcriptional activators. Initially, starvation-induced intracellular signals direct changes in gene expression. Subsequently, self-generated extracellular signals provide morphological cues that regulate certain transcriptional activators. However, signals for many of the activators remain to be discovered. A key insight is that activators often work combinatorially, allowing signal integration. The Myxococcus GRN differs strikingly from those governing sporulation of Bacillus and Streptomyces, suggesting Myxococcus evolved a highly signal-responsive GRN to enable complex multicellular development.

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“…Development is one example of multiscale emergent behavior in which molecular 2 interactions between cells allow self-organization into multicellular patterns. One of the 3 most remarkable features of all types of development is how robust it is in the face of 4 genetic and environmental perturbations, suggesting that backup systems are in 5 place [27]. While molecular genetics has identified mutations that impede multicellular 6 development, even single mutations create downstream effects that influence multiple 7 aspects of cell behavior and physiology.…”

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confidence: 99%

Data-driven models reveal mutant cell behaviors important for myxobacterial aggregation

Zhang

Cotter²,

Lyu³

et al. 2020

Preprint

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Single mutations frequently alter several aspects of cell behavior but it is often not clear whether a particular statistically significant change is biologically significant. To determine which behavioral changes are most important for multicellular self-organization, we devised a new methodology using Myxococcus xanthus as a model system. During development, myxobacteria coordinate their movement to aggregate into spore-filled fruiting bodies. We investigate how aggregation is restored in two mutants, csgA and pilC, that cannot aggregate unless mixed with wild type (WT) cells. To this end, we use cell tracking to follow movement of fluorescently labeled cells in combination with data-driven agent-based modeling. The results indicate that just like WT cells, both mutants bias their movement toward aggregates and reduce motility inside aggregates. However, several aspects of mutant behavior remain uncorrected by WT demonstrating that perfect recreation of WT behavior is unnecessary. In fact, synergies between errant behaviors can make aggregation robust. 12 partial rescue of the mutants during multicellular development of Myxococcus xanthus 13 biofilms. 14 Myxococcus xanthus is a rod-shaped member of the delta-Protobacteria with a 15 lifecycle centered around surface motility of cells in a biofilm. M. xanthus has evolved 16 1/20multiple social mechanisms such as S-motility [11] and C-signaling [5, 17, 26] to achieve 17 coordinated group behaviors such as predation [25], rippling [3,12,28] and 18 development [28,35]. Upon amino acid limitation, M. xanthus cells move into 19 three-dimensional aggregates called fruiting bodies where they sporulate [14,18,23]. 20 Recent studies based on cell tracking have provided unprecedented detail of cell 21 movement during development [7]. In combination with mathematical modeling, these 22 datasets unambiguously identified individual cell behaviors that are essential for 23 42 help of A-motility system that uses a novel molecular motor and focal adhesion 43 complexes [9,21]. However, most S-system mutants fail to develop because they cannot 44 produce an extracellular matrix (ECM) that is both essential for S-motility and vital for 45 development. The ECM is required for some types of chemotaxis [15,16] as well as for 46 cell cohesion, which could play a role in the inhibition of motility inside the 47 65 2/20 1 Results 66 1.1 Quantifying aggregation dynamics in mixtures of wild-type 67 and mutant strains 68 Fluorescence microscopy was used to quantify the behavior of mutant cells at both 69 single cell and population levels. A small fraction of cells expressing the fluorescent 70 protein tdTomato were mixed with cells expressing eYFP. Each cell expressing 71 tdTomato is bright enough to be segmented and tracked, allowing quantification of their 72 behaviors, whereas the weaker eYFP signal was used to quantify cell density during 73 aggregate growth [7]. 74 When either pilC or csgA cells are mixed with differentially labeled cells of their 75 own genotype, no aggregates were o...

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Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases

Cited by 46 publications

References 67 publications

Systematic analysis of the Myxococcus xanthus developmental gene regulatory network supports posttranslational regulation of FruA by C‐signaling

Systematic analysis of the Myxococcus xanthus developmental gene regulatory network supports posttranslational regulation of FruA by C‐signaling

Highly Signal-Responsive Gene Regulatory Network Governing Myxococcus Development

Data-driven models reveal mutant cell behaviors important for myxobacterial aggregation

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