Blebbing of Dictyostelium cells in response to chemoattractant

Langridge, Paul; Kay, Robert R.

doi:10.1016/j.yexcr.2006.03.007

Cited by 83 publications

(103 citation statements)

References 42 publications

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“…All these factors can be regulated independently, which can explain how cells such as Dictyostelium, which have a relatively high tension [up to 4,000 pN/μm (29)], do not form blebs bigger than about 10% of the cellular volume (39).…”

Section: Above a Critical Tension Bleb Size Increases With Increasinmentioning

confidence: 99%

Role of cortical tension in bleb growth

Tinévez

Schulze

Salbreux³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

512

575

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Blebs are spherical membrane protrusions often observed during cell migration, cell spreading, cytokinesis, and apoptosis, both in cultured cells and in vivo. Bleb expansion is thought to be driven by the contractile actomyosin cortex, which generates hydrostatic pressure in the cytoplasm and can thus drive herniations of the plasma membrane. However, the role of cortical tension in bleb formation has not been directly tested, and despite the importance of blebbing, little is known about the mechanisms of bleb growth. In order to explore the link between cortical tension and bleb expansion, we induced bleb formation on cells with different tensions. Blebs were nucleated in a controlled manner by laser ablation of the cortex, mimicking endogenous bleb nucleation. Cortical tension was modified by treatments affecting the level of myosin activity or proteins regulating actin turnover. We show that there is a critical tension below which blebs cannot expand. Above this threshold, the maximal size of a bleb strongly depends on tension, and this dependence can be fitted with a model of the cortex as an active elastic material. Together, our observations and model allow us to relate bleb shape parameters to the underlying cellular mechanics and provide insights as to how bleb formation can be biochemically regulated during cell motility.T he cell cortex is a thin meshwork of actin filaments, myosin, and associated proteins that lies beneath the plasma membrane (1). Because of the presence of active myosin motors, which slide filaments with respect to one another in the network, the cortex is under tension. As a result, the cortex exerts pressure on the cytoplasm and can actively contract, driving cell deformations (2).Blebs are spherical membrane protrusions that commonly occur at the cortex during cytokinesis, cell spreading, virus uptake, and apoptosis (3-7). Moreover, increasing evidence points to an essential role for blebs as leading edge protrusions during cell migration in three-dimensional environments, particularly during embryonic development and tumor-cell dissemination (8-11; reviewed in refs. 7, 12). Despite the importance of blebbing, very little is known about the mechanisms of bleb growth.The life cycle of a bleb can be subdivided into three phases (7, 13). First, a bleb is nucleated, either by local detachment of the cortex from the plasma membrane or by local rupture of the cortex. In the subsequent growth phase, a membrane bulge, initially devoid of cortex, expands from the nucleation site. Finally, the cortex gradually reassembles at the bleb membrane, leading to bleb retraction.Bleb formation is often correlated with high myosin II activity, and myosin II inhibition prevents blebbing (6,7,10,14). For that reason, and because of their round shape and rapid expansion, blebs are commonly believed to be a direct mechanical consequence of the hydrostatic pressure exerted on the cytoplasm by the contractile cortex, which would drive bleb growth from places of local cortex weakening without any further r...

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Section: Above a Critical Tension Bleb Size Increases With Increasinmentioning

confidence: 99%

Role of cortical tension in bleb growth

Tinévez

Schulze

Salbreux³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

512

575

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“…Bleb-like protrusions are a common form of cell migration in cells responding to chemotactic cues (Paluch et al 2006) and have recently been studied in zebrafish (Blaser et al 2006) and a variety of other systems (Charras et al 2005;Langridge and Kay 2006). In zebrafish, for example, the migration of germ cells is entirely mediated by blebbing (Blaser et al 2006).…”

Section: Gravin Acts Through Rhoa and Myosin II To Elicit Cell Shape mentioning

confidence: 99%

Gravin regulates mesodermal cell behavior changes required for axis elongation during zebrafish gastrulation

Weiser¹,

Pyati²,

Kimelman³

2007

Genes Dev.

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Convergent extension of the mesoderm is the major driving force of vertebrate gastrulation. During this process, mesodermal cells move toward the future dorsal side of the embryo, then radically change behavior as they initiate extension of the body axis. How cells make this transition in behavior is unknown. We have identified the scaffolding protein and tumor suppressor Gravin as a key regulator of this process in zebrafish embryos. We show that Gravin is required for the conversion of mesodermal cells from a highly migratory behavior to the medio-laterally intercalative behavior required for body axis extension. In the absence of Gravin, paraxial mesodermal cells fail to shut down the protrusive activity mediated by the Rho/ROCK/ Myosin II pathway, resulting in embryos with severe extension defects. We propose that Gravin functions as an essential scaffold for regulatory proteins that suppress the migratory behavior of the mesoderm during gastrulation, and suggest that this function also explains how Gravin inhibits invasive behaviors in metastatic cells.[Keywords: AKAP; convergence and extension; gastrulation; Gravin; Rho; zebrafish] Supplemental material is available at http://www.genesdev.org. Vertebrate gastrulation involves a tightly regulated series of cellular rearrangements that coordinate the movements of the three germ layers (endoderm, mesoderm, and ectoderm) to establish the final embryonic body plan (Keller 2002). This process requires a very precise regulation of cell polarity, cell migration, and cell division. One of the major driving forces of vertebrate gastrulation is convergent extension, a mechanism in which mesodermal cells move toward the future dorsal side of the embryo and then intercalate between neighboring cells, resulting in an overall dorsoventral narrowing (convergence) and anteroposterior lengthening (extension) of the embryo (Heisenberg and Tada 2002;Keller 2002; SolnicaKrezel 2006).Mesodermal cells in the zebrafish embryo involved in convergent extension undergo a series of changes starting with a slow dorsal-directed migration, a faster migration as they get closer to the future dorsal side, and then intercalation as they approach the dorsal midline (Concha and Adams 1998; Jessen et al. 2002;Solnica-Krezel 2006). As the mesodermal cells change their behaviors, they undergo a series of morphological changes in cell shape and protrusive activity (Concha and Adams 1998). During early gastrulation, mesodermal cells have an overall rounded phenotype and extend transient lamellipodia and bleb-like protrusions with random orientation (Concha and Adams 1998;. By mid-to late gastrulation, cells become more polarized with lamellipodia that become stabilized and mediolaterally oriented. These cells then migrate in a highly dorsally biased manner. Later in gastrulation, mesodermal cells become tightly packed on the dorsal side of the embryo. These cells, through contact inhibition of migratory behavior, become elongated and firmly attached to their neighboring cells, reduce protrusions,...

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“…Many moving cells can change shape radically as they move. For instance, Dictyostelium cells can expand their leading edge by myosin II-dependent blebbing (Yoshida and Inouye, 2001;Yoshida and Soldati, 2006;Langridge and Kay, 2006) and they alternate between rounded and elongated morphologies as they move (Wessels et al, 1998), with pseudopodia often projected from the front before the rear is withdrawn (Weber et al, 1995). Geometrical considerations suggest that these behaviours may produce transient increases in surface area, though this has not been quantified.…”

Section: Introductionmentioning

confidence: 99%

Possible roles of the endocytic cycle in cell motility

Traynor

Kay

2007

Journal of Cell Science

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Starving, highly motile Dictyostelium cells maintain an active endocytic cycle, taking up their surface about every 11 minutes. Cell motility depends on a functional NSF (N-ethylmaleimide sensitive factor) protein - also essential for endocytosis and membrane trafficking generally - and we, therefore, investigated possible ways in which the endocytic cycle might be required for cell movement. First, NSF, and presumably membrane trafficking, are not required for the initial polarization of the leading edge in a cyclic-AMP gradient. Second, we can detect no evidence for membrane flow from the leading edge, as photobleached or photoactivated marks in the plasma membrane move forward roughly in step with the leading edge, rather than backwards from it. Third, we find that the surface area of a cell - measured from confocal reconstructions - constantly fluctuates during movement as it projects pseudopodia and otherwise changes shape; increases of 20-30% can often occur over a few minutes. These fluctuations cannot be explained by reciprocal changes in filopodial surface area and they substantially exceed the 2-3% by which membranes can stretch. We propose that the endocytic cycle has a key function in motility by allowing adjustment of cell surface area to match changes in shape and that, without this function, movement is severely impaired.

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Blebbing of Dictyostelium cells in response to chemoattractant

Cited by 83 publications

References 42 publications

Role of cortical tension in bleb growth

Role of cortical tension in bleb growth

Gravin regulates mesodermal cell behavior changes required for axis elongation during zebrafish gastrulation

Possible roles of the endocytic cycle in cell motility

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