RESUMO
Cell motility universally relies on spatial regulation of focal adhesion complexes (FAs) connecting the substrate to cellular motors. In bacterial FAs, the Adventurous gliding motility machinery (Agl-Glt) assembles at the leading cell pole following a Mutual gliding-motility protein (MglA)-guanosine 5'-triphosphate (GTP) gradient along the cell axis. Here, we show that GltJ, a machinery membrane protein, contains cytosolic motifs binding MglA-GTP and AglZ and recruiting the MreB cytoskeleton to initiate movement toward the lagging cell pole. In addition, MglA-GTP binding triggers a conformational shift in an adjacent GltJ zinc-finger domain, facilitating MglB recruitment near the lagging pole. This prompts GTP hydrolysis by MglA, leading to complex disassembly. The GltJ switch thus serves as a sensor for the MglA-GTP gradient, controlling FA activity spatially.
Assuntos
Proteínas de Bactérias , Adesões Focais , Guanosina Trifosfato , Adesões Focais/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Guanosina Trifosfato/metabolismo , Ligação ProteicaRESUMO
Hydraulic fracturing plays a major role in cavity formation during embryonic development, when pressurized fluid opens microlumens at cell-cell contacts, which evolve to form a single large lumen. However, the fundamental physical mechanisms behind these processes remain masked by the complexity and specificity of biological systems. Here, we show that adhered lipid vesicles subjected to osmotic stress form hydraulic microlumens similar to those in cells. Combining vesicle experiments with theoretical modelling and numerical simulations, we provide a physical framework for the hydraulic reconfiguration of cell-cell adhesions. We map the conditions for microlumen formation from a pristine adhesion, the emerging dynamical patterns and their subsequent maturation. We demonstrate control of the fracturing process depending on the applied pressure gradients and the type and density of membrane bonds. Our experiments further reveal an unexpected, passive transition of microlumens to closed buds that suggests a physical route to adhesion remodeling by endocytosis.
Assuntos
Endocitose , Adesão Celular , Fenômenos FísicosRESUMO
In a recent study, Wang et al. (https://doi.org/10.1083/jcb.202206074) demonstrate that subtle differences between two ADF/cofilin isoforms allow fine spatial regulation of the actin cytoskeleton in pollen tubes. This article illustrates how two similar proteins have progressively evolved to adapt their localization and activity according to the cellular environment.
Assuntos
Fatores de Despolimerização de Actina , Proteínas dos Microfilamentos , Tubo Polínico , Citoesqueleto de Actina/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Tubo Polínico/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Força Próton-MotrizRESUMO
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.
Assuntos
Proteínas de Bactérias , Movimento Celular , Myxococcus xanthus , Proteínas ras , Myxococcus xanthus/citologia , Myxococcus xanthus/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Transdução de Sinais , Proteínas ras/química , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Modelos BiológicosRESUMO
Social bacteria display complex behaviours whereby thousands of cells collectively and dramatically change their form and function in response to nutrient availability and changing environmental conditions. In this review, we focus on Myxococcus xanthus motility, which supports spectacular transitions based on prey availability across its life cycle. A large body of work suggests that these behaviours require sensory capacity implemented at the single-cell level. Focusing on recent genetic work on a core cellular pathway required for single-cell directional decisions, we argue that signal integration, multi-modal sensing and memory are at the root of decision making leading to multicellular behaviours. Hence, Myxococcus may be a powerful biological system to elucidate how cellular building blocks cooperate to form sensory multicellular assemblages, a possible origin of cognitive mechanisms in biological systems. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.
Assuntos
Interações Microbianas/fisiologia , Myxococcus xanthus/fisiologiaRESUMO
Mechanosensing by T cells through the T cell receptor (TCR) is at the heart of immune recognition. While the mechanobiology of the TCR at the molecular level is increasingly well documented, its link to cell-scale response is poorly understood. Here we explore T cell spreading response as a function of substrate rigidity and show that remarkably, depending on the surface receptors stimulated, the cellular response may be either biphasic or monotonous. When adhering solely via the TCR complex, T cells respond to environmental stiffness in an unusual fashion, attaining maximal spreading on an optimal substrate stiffness comparable to that of professional antigen-presenting cells. However, in the presence of additional ligands for the integrin LFA-1, this biphasic response is abrogated and the cell spreading increases monotonously with stiffness up to a saturation value. This ligand-specific mechanosensing is effected through an actin-polymerization-dependent mechanism. We construct a mesoscale semianalytical model based on force-dependent bond rupture and show that cell-scale biphasic or monotonous behavior emerges from molecular parameters. As the substrate stiffness is increased, there is a competition between increasing effective stiffness of the bonds, which leads to increased cell spreading and increasing bond breakage, which leads to decreased spreading. We hypothesize that the link between actin and the receptors (TCR or LFA-1), rather than the ligand/receptor linkage, is the site of this mechanosensing.