scholarly journals Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration

Science ◽  
2020 ◽  
Vol 368 (6496) ◽  
pp. 1205-1210 ◽  
Author(s):  
Anjali Bisaria ◽  
Arnold Hayer ◽  
Damien Garbett ◽  
Daniel Cohen ◽  
Tobias Meyer
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Cell Polarization ◽  
Density Gradients ◽  
Membrane Protrusion ◽  
Fluorescent Reporter ◽  
Membrane Protrusions ◽  
Directed Polymerization ◽  
Actin Concentration ◽  
Migrating Cells

Cell migration is driven by local membrane protrusion through directed polymerization of F-actin at the front. However, F-actin next to the plasma membrane also tethers the membrane and thus resists outgoing protrusions. Here, we developed a fluorescent reporter to monitor changes in the density of membrane-proximal F-actin (MPA) during membrane protrusion and cell migration. Unlike the total F-actin concentration, which was high in the front of migrating cells, MPA density was low in the front and high in the back. Back-to-front MPA density gradients were controlled by higher cofilin-mediated turnover of F-actin in the front. Furthermore, nascent membrane protrusions selectively extended outward from areas where MPA density was reduced. Thus, locally low MPA density directs local membrane protrusions and stabilizes cell polarization during cell migration.

scholarly journals Membrane proximal F-actin restricts local membrane protrusions and directs cell migration

2019 ◽  
Author(s):  
Anjali Bisaria ◽  
Arnold Hayer ◽  
Damien Garbett ◽  
Daniel Cohen ◽  
Tobias Meyer
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Actin Polymerization ◽  
Cell Polarization ◽  
Structural Parameter ◽  
Low Density ◽  
Membrane Protrusion ◽  
Fluorescent Reporter ◽  
Membrane Protrusions ◽  
Actin Concentration

AbstractA major component of cell migration is F-actin polymerization driven membrane protrusion in the front. However, F-actin proximal to the plasma membrane also has a scaffolding role to support and attach the membrane. Here we developed a fluorescent reporter to monitor changes in the density of membrane proximal F-actin during membrane protrusion and cell migration. Strikingly, unlike total F-actin concentration, which is high in the front of migrating cells, the density of membrane proximal F-actin is low in the front and high in the back. Furthermore, local membrane protrusions only form following local decreases in membrane proximal F-actin density. Our study suggests that low density of membrane proximal F-actin is a fundamental structural parameter that locally directs membrane protrusions and globally stabilizes cell polarization during cell migration.One Sentence SummaryMembrane protrusion and cell migration are directed by local decreases in the density of membrane proximal F-actin

scholarly journals So far, yet so close: α-Catenin dimers help migrating cells get together

2017 ◽  
Vol 216 (11) ◽  
pp. 3437-3439
Author(s):  
Laura Machesky ◽  
Vania M.M. Braga
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Active Plasma ◽  
Cell Biol ◽  
Membrane Protrusions ◽  
Freely Moving ◽  
And Migration ◽  
Migrating Cells

Epithelial cells in tissues use their actin cytoskeletons to stick together, whereas unattached cells make active plasma membrane protrusions to migrate. In this issue, Wood et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612006) show that the junction component α-catenin is critical in freely moving cells to promote adhesion and migration.

scholarly journals T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Damien Garbett ◽  
Anjali Bisaria ◽  
Changsong Yang ◽  
Dannielle G. McCarthy ◽  
Arnold Hayer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Actin Filaments ◽  
Myosin Ii ◽  
Adhesion Sites ◽  
Membrane Protrusions ◽  
And Migration ◽  
Muscle Myosin ◽  
Migrating Cells

Abstract Migrating cells move across diverse assemblies of extracellular matrix (ECM) that can be separated by micron-scale gaps. For membranes to protrude and reattach across a gap, actin filaments, which are relatively weak as single filaments, must polymerize outward from adhesion sites to push membranes towards distant sites of new adhesion. Here, using micropatterned ECMs, we identify T-Plastin, one of the most ancient actin bundling proteins, as an actin stabilizer that promotes membrane protrusions and enables bridging of ECM gaps. We show that T-Plastin widens and lengthens protrusions and is specifically enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity. Together, our study uncovers critical roles of the actin bundler T-Plastin to promote protrusions and migration when adhesion is spatially-gapped.

scholarly journals Actin dynamics in cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 483-495 ◽  
Author(s):  
Matthias Schaks ◽  
Grégory Giannone ◽  
Klemens Rottner
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Actin Filament ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Actin Dynamics ◽  
Regulatory Complex ◽  
Membrane Protrusions ◽  
Filament Networks ◽  
Contractile Forces

Abstract Cell migration is an essential process, both in unicellular organisms such as amoeba and as individual or collective motility in highly developed multicellular organisms like mammals. It is controlled by a variety of activities combining protrusive and contractile forces, normally generated by actin filaments. Here, we summarize actin filament assembly and turnover processes, and how respective biochemical activities translate into different protrusion types engaged in migration. These actin-based plasma membrane protrusions include actin-related protein 2/3 complex-dependent structures such as lamellipodia and membrane ruffles, filopodia as well as plasma membrane blebs. We also address observed antagonisms between these protrusion types, and propose a model – also inspired by previous literature – in which a complex balance between specific Rho GTPase signaling pathways dictates the protrusion mechanism employed by cells. Furthermore, we revisit published work regarding the fascinating antagonism between Rac and Rho GTPases, and how this intricate signaling network can define cell behavior and modes of migration. Finally, we discuss how the assembly of actin filament networks can feed back onto their regulators, as exemplified for the lamellipodial factor WAVE regulatory complex, tightly controlling accumulation of this complex at specific subcellular locations as well as its turnover.

scholarly journals MYADM regulates Rac1 targeting to ordered membranes required for cell spreading and migration

2011 ◽  
Vol 22 (8) ◽  
pp. 1252-1262 ◽  
Author(s):  
Juan F. Aranda ◽  
Natalia Reglero-Real ◽  
Leonor Kremer ◽  
Beatriz Marcos-Ramiro ◽  
Ana Ruiz-Sáenz ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Mammalian Cells ◽  
Cell Spreading ◽  
Membrane Domains ◽  
Membrane Raft ◽  
General Process ◽  
Membrane Protrusions ◽  
Differentiation Marker ◽  
And Migration

Membrane organization into condensed domains or rafts provides molecular platforms for selective recruitment of proteins. Cell migration is a general process that requires spatiotemporal targeting of Rac1 to membrane rafts. The protein machinery responsible for making rafts competent to recruit Rac1 remains elusive. Some members of the MAL family of proteins are involved in specialized processes dependent on this type of membrane. Because condensed membrane domains are a general feature of the plasma membrane of all mammalian cells, we hypothesized that MAL family members with ubiquitous expression and plasma membrane distribution could be involved in the organization of membranes for cell migration. We show that myeloid-associated differentiation marker (MYADM), a protein with unique features within the MAL family, colocalizes with Rac1 in membrane protrusions at the cell surface and distributes in condensed membranes. MYADM knockdown (KD) cells had altered membrane condensation and showed deficient incorporation of Rac1 to membrane raft fractions and, similar to Rac1 KD cells, exhibited reduced cell spreading and migration. Results of rescue-of-function experiments by expression of MYADM or active Rac1L61 in cells knocked down for Rac1 or MYADM, respectively, are consistent with the idea that MYADM and Rac1 act on parallel pathways that lead to similar functional outcomes.

scholarly journals Integrin-mediated Adhesion Regulates Cell Polarity and Membrane Protrusion through the Rho Family of GTPases

2001 ◽  
Vol 12 (2) ◽  
pp. 265-277 ◽  
Author(s):  
Elisabeth A. Cox ◽  
Sarita K. Sastry ◽  
Anna Huttenlocher
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Cross Talk ◽  
Cell Polarization ◽  
Stop Signal ◽  
Membrane Protrusion ◽  
Rhoa Activity ◽  
Rac1 Activity ◽  
Rho Family ◽  
Α5β1 Integrin

Integrin-mediated adhesion is a critical regulator of cell migration. Here we demonstrate that integrin-mediated adhesion to high fibronectin concentrations induces a stop signal for cell migration by inhibiting cell polarization and protrusion. On fibronectin, the stop signal is generated through α5β1 integrin-mediated signaling to the Rho family of GTPases. Specifically, Cdc42 and Rac1 activation exhibits a biphasic dependence on fibronectin concentration that parallels optimum cell polarization and protrusion. In contrast, RhoA activity increases with increasing substratum concentration. We find that cross talk between Cdc42 and Rac1 is required for substratum-stimulated protrusion, whereas RhoA activity is inhibitory. We also show that Cdc42 activity is inhibited by Rac1 activation, suggesting that Rac1 activity may down-regulate Cdc42 activity and promote the formation of stabilized rather than transient protrusion. Furthermore, expression of RhoA down-regulates Cdc42 and Rac1 activity, providing a mechanism whereby RhoA may inhibit cell polarization and protrusion. These findings implicate adhesion-dependent signaling as a mechanism to stop cell migration by regulating cell polarity and protrusion via the Rho family of GTPases.

scholarly journals Proteolysis of Cortactin by Calpain Regulates Membrane Protrusion during Cell Migration

2006 ◽  
Vol 17 (1) ◽  
pp. 239-250 ◽  
Author(s):  
Benjamin J. Perrin ◽  
Kurt J. Amann ◽  
Anna Huttenlocher
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Biochemical Properties ◽  
Actin Binding ◽  
Potential Candidate ◽  
Membrane Protrusion ◽  
Cortical Actin ◽  
Membrane Protrusions ◽  
Src Homology ◽  
Calpain 2

Calpain 2 regulates membrane protrusion during cell migration. However, relevant substrates that mediate the effects of calpain on protrusion have not been identified. One potential candidate substrate is the actin binding protein cortactin. Cortactin is a Src substrate that drives actin polymerization by activating the Arp2/3 complex and also stabilizes the cortical actin network. We now provide evidence that proteolysis of cortactin by calpain 2 regulates membrane protrusion dynamics during cell migration. We show that cortactin is a calpain 2 substrate in fibroblasts and that the preferred cleavage site occurs in a region between the actin binding repeats and the α-helical domain. We have generated a mutant cortactin that is resistant to calpain proteolysis but retains other biochemical properties of cortactin. Expression of the calpain-resistant cortactin, but not wild-type cortactin, impairs cell migration and increases transient membrane protrusion, suggesting that calpain proteolysis of cortactin limits membrane protrusions and regulates migration in fibroblasts. Furthermore, the enhanced protrusion observed with the calpain-resistant cortactin requires both the Arp2/3 binding site and the Src homology 3 domain of cortactin. Together, these findings suggest a novel role for calpain-mediated proteolysis of cortactin in regulating membrane protrusion dynamics during cell migration.

scholarly journals The formin FMNL3 assembles plasma membrane protrusions that participate in cell–cell adhesion

2015 ◽  
Vol 26 (3) ◽  
pp. 467-477 ◽  
Author(s):  
Timothy J. Gauvin ◽  
Lorna E. Young ◽  
Henry N. Higgs
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Cellular Localization ◽  
Cell Contact ◽  
Contact Sites ◽  
Culture Cells ◽  
Membrane Protrusions ◽  
Punctate Pattern ◽  
Cell Cell

FMNL3 is a vertebrate-specific formin protein previously shown to play a role in angiogenesis and cell migration. Here we define the cellular localization of endogenous FMNL3, the dynamics of GFP-tagged FMNL3 during cell migration, and the effects of FMNL3 suppression in mammalian culture cells. The majority of FMNL3 localizes in a punctate pattern, with >95% of these puncta being indistinguishable from the plasma membrane by fluorescence microscopy. A small number of dynamic cytoplasmic FMNL3 patches also exist, which enrich near cell–cell contact sites and fuse with the plasma membrane at these sites. These cytoplasmic puncta appear to be part of larger membranes of endocytic origin. On the plasma membrane, FMNL3 enriches particularly in filopodia and membrane ruffles and at nascent cell–cell adhesions. FMNL3-containing filopodia occur both at the cell–substratum interface and at cell–cell contacts, with the latter being 10-fold more stable. FMNL3 suppression by siRNA has two major effects: decrease in filopodia and compromised cell–cell adhesion in cells migrating as a sheet. Overall our results suggest that FMNL3 functions in assembly of actin-based protrusions that are specialized for cell–cell adhesion.

Sign in / Sign up

Export Citation Format

Share Document