MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus

Galicia, Christian; Lhospice, Sébastien; Varela, Paloma F.; Trapani, Stefano; Zhang, Wenhua; Navaza, Jorge; Herrou, Julien; Mignot, Tâm; Cherfils, Jacqueline

doi:10.1038/s41467-019-13274-3

Cited by 30 publications

(64 citation statements)

References 48 publications

(80 reference statements)

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“…A similar observation was reported for Thermus thermophilus MglA and MglB, where MglB interacts strongly with only GTP‐bound MglA [27]. MglB interacts with MxMglA‐GDP and functions as a GEF for MxMglA by facilitating the exchange of GDP [16], in contrast to another report where GEF activity by MglB has not been observed for MxMglA [17]. Our mant ‐GDP exchange measurements in the presence of MglB under similar reaction conditions as that reported for MxMglA [16] confirm that MglB does not function as a GEF for SofG ∆60 (Fig.…”

Section: Discussionsupporting

confidence: 77%

“…MglB (36 kDa dimer) is known to elute anomalously at a molecular weight higher than expected (~ 52 kDa; Fig. 3D,E) [16,17,27]. Hence, the elution volume for the complex of SofG ∆60 and MglB (expected: 63 kDa) coincides with that of MglB dimer alone.…”

Section: Methodsmentioning

confidence: 74%

“…Recently, we demonstrated that MglB, the cognate GAP of MglA, functions also as a GEF for MglA, by accelerating GDP exchange from MglA [16]. In contrast to this report, GEF activity by MglB has not been observed for MglA in another report under a different set of reaction conditions [17]. RomRX is another protein complex that performs a GEF function for MglA [18].…”

Section: Introductionmentioning

confidence: 80%

“…Cell polarity determination and polarity reversals of M. xanthus in response to these environmental cues are regulated by a small Ras‐like GTPase MglA and its GAP MglB. These proteins have been structurally and biochemically characterized, as reported from studies in Thermus thermophilus (Tt) and Myxococcus xanthus (Mx) proteins [15–17]. Recently, we demonstrated that MglB, the cognate GAP of MglA, functions also as a GEF for MglA, by accelerating GDP exchange from MglA [16].…”

Section: Introductionmentioning

confidence: 99%

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Dual specificity of a prokaryotic GTPase‐activating protein (GAP) to two small Ras‐like GTPases inMyxococcus xanthus

et al. 2020

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Two small Ras‐like GTPases, MglA and SofG, work in synchrony to drive cell polarity and motility in the soil bacterium, Myxococcus xanthus. While MglA regulates two types of motility in Myxococcus and drives cell polarity reversals, SofG regulates social motility enabled by the type IV pili (T4P) machinery. In order to understand the molecular basis of how multiple GTPases act concertedly, we initiated biochemical studies on SofG. A construct of SofG (SofG∆60) was purified as a homogenous monomer and could bind to GDP and GTP. Intrinsic GTP hydrolysis by SofG∆60 was negligible. Earlier work from the laboratory revealed that MglB functions both as a GTPase‐activating protein (GAP) and a guanine nucleotide exchange factor (GEF) for MglA. Biochemical assays of SofG∆60 established that MglB interacts with GTP‐bound SofG∆60 and acts as a GAP for SofG∆60. Interaction of MglB with SofG∆60 in the GDP‐bound conformation was not observed, thereby suggesting that MglB might not act as a GEF for SofG∆60. The existence of a common GAP for both SofG and MglA could potentially contribute to concerted regulation of their GTPase activities, and mediate crosstalk between the two GTPases involved in motility of M. xanthus. Sequence analysis revealed the features for a SofG‐like subclass of prokaryotic small Ras‐like GTPases that enable MglB to act as a dual‐specificity GAP.

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Section: Discussionsupporting

confidence: 77%

Section: Methodsmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Dual specificity of a prokaryotic GTPase‐activating protein (GAP) to two small Ras‐like GTPases inMyxococcus xanthus

et al. 2020

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“…3a, Supplementary Video 7). These were reminiscent of oscillations in the twitching and gliding regulators observed in M. xanthus 21,26,27 . The proportion of cells exhibiting these oscillations became smaller after prolonged surface contact (Fig.…”

Section: Supplementary Video 5) While Mng-mentioning

confidence: 71%

Mechanotaxis directsPseudomonas aeruginosatwitching motility

Talà

Kühn

Inclán

et al. 2021

Preprint

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The opportunistic pathogen Pseudomonas aeruginosa explores surfaces using twitching motility powered by retractile extracellular filaments called type IV pili. Single cells twitch by successive pili extension, attachment and retraction. However, whether and how single cells control twitching migration remains unclear. We discovered that P. aeruginosa actively directs twitching in the direction of mechanical input from type IV pili, in a process we call mechanotaxis. The Chp chemotaxis-like system controls the balance of forward and reverse twitching migration of single cells in response to the mechanical signal. On surfaces, Chp senses type IV pili attachment at one pole thereby sensing a spatially-resolved signal. As a result, the Chp response regulators PilG and PilH control the polarization of the extension motor PilB. PilG stimulates polarization favoring forward migration, while PilH inhibits polarization inducing reversal. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. This distinct localization of response regulators establishes a signaling landscape known as local-excitation, global-inhibition in higher order organisms, identifying a conserved strategy to transduce spatially-resolved signals. Our discovery finally resolves the function of the Chp system and expands our view of the signals regulating motility.

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Unorthodox regulation of the MglA Ras‐like GTPase controlling polarity in Myxococcus xanthus

Dinet

Mignot

2023

FEBS Letters

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Motile cells have developed a large array of molecular machineries to actively change their direction of movement in response to spatial cues from their environment. In this process, small GTPases act as molecular switches and work in tandem with regulators and sensors of their guanine nucleotide status (GAP, GEF, GDI and effectors) to dynamically polarize the cell and regulate its motility. In this review, we focus on Myxococcus xanthus as a model organism to elucidate the function of an atypical small Ras GTPase system in the control of directed cell motility. M. xanthus cells direct their motility by reversing their direction of movement through a mechanism involving the redirection of the motility apparatus to the opposite cell pole. The reversal frequency of moving M. xanthus cells is controlled by modular and interconnected protein networks linking the chemosensory‐like frizzy (Frz) pathway – that transmits environmental signals – to the downstream Ras‐like Mgl polarity control system – that comprises the Ras‐like MglA GTPase protein and its regulators. Here, we discuss how variations in the GTPase interactome landscape underlie single‐cell decisions and consequently, multicellular patterns.

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MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus

Cited by 30 publications

References 48 publications

Dual specificity of a prokaryotic GTPase‐activating protein (GAP) to two small Ras‐like GTPases inMyxococcus xanthus

Dual specificity of a prokaryotic GTPase‐activating protein (GAP) to two small Ras‐like GTPases inMyxococcus xanthus

Mechanotaxis directsPseudomonas aeruginosatwitching motility

Unorthodox regulation of the MglA Ras‐like GTPase controlling polarity in Myxococcus xanthus

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