Filopodium retraction is controlled by adhesion to its tip

Roméro, Stéphane; Quatela, Alessia; Bornschlögl, Thomas; Guadagnini, Stéphanie; Bassereau, Patricia; Nhieu, Guy Tran Van

doi:10.1242/jcs.104778

Cited by 40 publications

(31 citation statements)

References 34 publications

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“…Filopodial tip adhesions regulate filopodial contractility and the generation of traction forces (Moore et al, 2009(Moore et al, , 2012Romero et al, 2013). We find that Fmn2-depleted filopodia are severely compromised in their ability to generate traction forces, possibly owing to impaired engagement of the cytoskeleton with the ECM.…”

Section: Discussionmentioning

confidence: 78%

“…The importance of tip adhesions has been highlighted in recent studies on filopodial traction forces (Bornschlögl et al, 2013;Chan and Odde, 2008;Hoffmann and Schäfer, 2010;Romero et al, 2013). Our observation of reduced pFAK signal in Fmn2 morphant filopodial tips prompted us to investigate filopodial traction.…”

Section: Fmn2 Depletion Impairs Traction Generation By the Filopodialmentioning

confidence: 80%

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Formin-2 regulates stabilization of filopodial tip adhesions in growth cones and affects neuronal outgrowth and pathfinding in vivo

et al. 2015

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Growth cone filopodia are actin-based mechanosensory structures that are essential for chemoreception and the generation of contractile forces necessary for directional motility. However, little is known about the influence of filopodial actin structures on substrate adhesion and filopodial contractility. Formin 2 (Fmn2) localizes along filopodial actin bundles and its depletion does not affect filopodia initiation or elongation. However, Fmn2 activity is required for filopodial tip adhesion maturation and the ability of filopodia to generate traction forces. Dysregulation of filopodia in Fmn2-depleted neurons leads to compromised growth cone motility. Additionally, in mouse fibroblasts, Fmn2 regulates ventral stress fiber assembly and affects the stability of focal adhesions. In the developing chick spinal cord, Fmn2 activity is required cellautonomously for the outgrowth and pathfinding of spinal commissural neurons. Our results reveal an unanticipated function for Fmn2 in neural development. Fmn2 regulates structurally diverse bundled actin structures, parallel filopodial bundles in growth cones and anti-parallel stress fibers in fibroblasts, in turn modulating the stability of substrate adhesions. We propose Fmn2 as a mediator of actin bundle integrity, enabling efficient force transmission to the adhesion sites.

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Section: Discussionmentioning

confidence: 78%

Section: Fmn2 Depletion Impairs Traction Generation By the Filopodialmentioning

confidence: 80%

Formin-2 regulates stabilization of filopodial tip adhesions in growth cones and affects neuronal outgrowth and pathfinding in vivo

et al. 2015

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“…Retraction of filopodia can be induced by attaching beads to their tips and counteracting mechanical forces can stall or even invert filopodial retraction (16,25,30). To better understand the mechanism and the dynamics of filopodial retraction against force we analyzed the dependency of retraction speed on counteracting forces, using the experimental setup shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Filopodial retraction force is generated by cortical actin dynamics and controlled by reversible tethering at the tip

Bornschlögl

Roméro

Vestergaard

et al. 2013

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

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136

109

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Filopodia are dynamic, finger-like plasma membrane protrusions that sense the mechanical and chemical surroundings of the cell. Here, we show in epithelial cells that the dynamics of filopodial extension and retraction are determined by the difference between the actin polymerization rate at the tip and the retrograde flow at the base of the filopodium. Adhesion of a bead to the filopodial tip locally reduces actin polymerization and leads to retraction via retrograde flow, reminiscent of a process used by pathogens to invade cells. Using optical tweezers, we show that filopodial retraction occurs at a constant speed against counteracting forces up to 50 pN. Our measurements point toward retrograde flow in the cortex together with frictional coupling between the filopodial and cortical actin networks as the main retraction-force generator for filopodia. The force exerted by filopodial retraction, however, is limited by the connection between filopodial actin filaments and the membrane at the tip. Upon mechanical rupture of the tip connection, filopodia exert a passive retraction force of 15 pN via their plasma membrane. Transient reconnection at the tip allows filopodia to continuously probe their surroundings in a load-and-fail manner within a welldefined force range.cytoskeleton | mechanics | membrane-tension | pulling | lamellipodium

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“…Filopodia play an essential role during cell migration, cell-cell or cell-matrix adhesion, by initiating contacts and conveying signals to the cell cortex. Because their dynamics depend on a discrete number of actin filaments, filopodia provide a model of choice to study elementary events linked to adhesion and downstream signaling [33].…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 family proteins and cytoskeleton changes involved in DM-1 cytotoxic effect on melanoma cells

et al. 2013

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Melanoma is one of the most aggressive types of skin cancer and its incidence rate is still increasing. All existing treatments are minimally effective. Consequently, new therapeutic agents for melanoma treatment should be developed. The DM-1 compound is a curcumin analog that possesses several curcumin characteristics, such as antiproliferative, antitumor and antimetastatic properties. The aim of this study was to evaluate the different signaling pathways involved in the cytotoxic effect of DM-1 on melanoma cells.The apoptotic process and cytoskeletal changes were evaluated by immunoblotting and immunofluorescence, respectively, in melanoma cells.After DM-1 treatment, SK-MEL-5 melanoma cells showed actin filaments disorganization with spicules formation throughout the cytoskeleton and significant reduction of focal adhesion as well as they were present only at cell extremities, conferring a poor connection between the cell and the substrate. Besides this, there was significant filopodium retraction and loss of typical cytoskeleton scaffold. These modifications contributed to cell detachment followed by cell death.Furthermore, DM-1-induced apoptosis was triggered by multiple Bcl-2 proteins involved in both the extrinsic and the intrinsic apoptotic pathways. SK-MEL-5 cells showed a death mechanism mainly by Bcl-2/Bax ratio decrease, whereas A375 cells presented apoptosis induction by Mcl-1 and Bcl-xL downregulation. In SK-MEL-5 and A375 melanoma cells, there were a significant increase in the active form of caspase 9 and the inactive form of the effector caspase 3 was decreased in both cell lines. Expression of cleaved Parp was increased after DM-1 treatment in these melanoma cell lines, demonstrating 2 that the apoptotic process occurred. Altogether, these data elucidate the cellular and molecular mechanisms involved in the cytotoxicity induced by the antitumor agent DM-1 in melanoma cells.

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Filopodium retraction is controlled by adhesion to its tip

Cited by 40 publications

References 34 publications

Formin-2 regulates stabilization of filopodial tip adhesions in growth cones and affects neuronal outgrowth and pathfinding in vivo

Formin-2 regulates stabilization of filopodial tip adhesions in growth cones and affects neuronal outgrowth and pathfinding in vivo

Filopodial retraction force is generated by cortical actin dynamics and controlled by reversible tethering at the tip

Bcl-2 family proteins and cytoskeleton changes involved in DM-1 cytotoxic effect on melanoma cells

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