Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables

Kobielak, Agnieszka; Pasolli, H. Amalia; Fuchs, Elaine

doi:10.1038/ncb1075

Cited by 347 publications

(308 citation statements)

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“…We showed that Cdc42 and formin activities are the dominant signaling molecules that regulate cell adhesion on a 30-kPa Ecad-Fc PA gel during initial cell-cell adhesion in 2D and 3D. Therefore, it is possible that Cdc42-and formin-dependent actin polymerization supports high levels of strain exerted by opposing cells during early stages of cell-cell adhesion (8,67). During intermediate stages of cell-cell contact, when the area of the contact increases and E-cadherin is stabilized at the junction, strain and stress at the contact would redistribute as the contact expands (similar to the changes in stress distribution observed in 30-kPa and 60-kPa Ecad-Fc PA gels, Fig.…”

Section: Discussionmentioning

confidence: 98%

Changes in E-cadherin rigidity sensing regulate cell adhesion

Collins

Denisin

Pruitt

et al. 2017

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

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Mechanical cues are sensed and transduced by cell adhesion complexes to regulate diverse cell behaviors. Extracellular matrix (ECM) rigidity sensing by integrin adhesions has been well studied, but rigidity sensing by cadherins during cell adhesion is largely unexplored. Using mechanically tunable polyacrylamide (PA) gels functionalized with the extracellular domain of E-cadherin (Ecad-Fc), we showed that E-cadherin-dependent epithelial cell adhesion was sensitive to changes in PA gel elastic modulus that produced striking differences in cell morphology, actin organization, and membrane dynamics. Traction force microscopy (TFM) revealed that cells produced the greatest tractions at the cell periphery, where distinct types of actin-based membrane protrusions formed. Cells responded to substrate rigidity by reorganizing the distribution and size of hightraction-stress regions at the cell periphery. Differences in adhesion and protrusion dynamics were mediated by balancing the activities of specific signaling molecules. Cell adhesion to a 30-kPa Ecad-Fc PA gel required Cdc42-and formin-dependent filopodia formation, whereas adhesion to a 60-kPa Ecad-Fc PA gel induced Arp2/3-dependent lamellipodial protrusions. A quantitative 3D cell-cell adhesion assay and live cell imaging of cell-cell contact formation revealed that inhibition of Cdc42, formin, and Arp2/3 activities blocked the initiation, but not the maintenance of established cell-cell adhesions. These results indicate that the same signaling molecules activated by E-cadherin rigidity sensing on PA gels contribute to actin organization and membrane dynamics during cell-cell adhesion. We hypothesize that a transition in the stiffness of E-cadherin homotypic interactions regulates actin and membrane dynamics during initial stages of cellcell adhesion.C ell adhesion is essential for tissue structure and function. Cells use specialized types of adhesions to interact with the surrounding environment, including integrin-based focal adhesions at cell-extracellular matrix (cell-ECM) contacts and cadherin-based adhesions at cell-cell contacts (1). Integrins bind to the ECM and intracellular proteins that link to the actin cytoskeleton and important signaling pathways (2). Similarly, cadherins regulate cellcell recognition and adhesion (3) and, through cytoplasmic adaptor proteins (catenins, vinculin) (4, 5), also link to the actin cytoskeleton and other proteins with signaling and scaffolding functions (6).Initiation of cell-cell adhesion requires significant reorganization of the actin cytoskeleton and is tightly controlled by the activities of actin nucleating proteins and Rho GTPases. Adhesion is initiated when filopodia from opposing cells come into contact with one another (7,8), and this process is regulated by Cdc42 activity (9, 10) and formin-dependent actin polymerization (11)(12)(13)(14). Intermediate stages of cell-cell contact formation involve lateral expansion of the contact by Rac1-induced and Arp2/3-dependent lamellipodial activity (15, 16). Finally, com...

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Section: Discussionmentioning

confidence: 98%

Changes in E-cadherin rigidity sensing regulate cell adhesion

Collins

Denisin

Pruitt

et al. 2017

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

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“…They vary greatly in size, with some reaching enormous lengths of up to 0.5 mm and ranking second only to the special processes of neuronal cells, i.e., neurites. Their cytoskeletal core is essentially based on a system of actin microfilament bundles, fortified and attached to the cell membrane via myosin, α-actinin, ezrin, and probably other morphogenic actin-binding proteins that have yet to be identified (for candidates see, e.g., Bonilha et al 1999;Vaheri et al 1997;Bretscher et al 2002;Kobielak et al 2004) and of microtubules (cf. Fig.…”

Section: Discussionmentioning

confidence: 99%

Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells

et al. 2007

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Substrate-adherent cultured cells derived from human bone marrow or umbilical cord blood ("mesenchymal stem cells") are of special interest for regenerative medicine. We report that such cells, which can display considerable heterogeneity with respect to their cytoskeletal protein complement, are often interconnected by special tentacle-like cell processes contacting one or several other cells. These processus adhaerentes, studded with many (usually small) puncta adhaerentia and varying greatly in length (up to more than 400 μm long), either contact each other in the intercellular space ("ET touches") or insert in a tight-fitting manner into deep plasma membrane invaginations (recessus adhaerentes), thus forming a novel kind of long (up to 50 μm) continuous cuff-like junction (manubria adhaerentia). The cell processes contain an actin microfilament core that is stabilized with ezrin, α-actinin, and myosin and accompanied by microtubules, and their adhering junctions are characterized by a molecular complement comprising the transmembrane glycoproteins N-cadherin and cadherin-11, in combination with the cytoplasmic plaque proteins α-and β-catenin, together with p120 ctn , plakoglobin, and afadin. The processes are also highly dynamic and rapidly foreshorten as cell colonies approach a denser state of cell packing. These structures are obviously able to establish cell-cell connections, even over long distances, and can form deep-rooted and tight cell-cell adhesions. The possible relationship to similar cell processes in the embryonic primary mesenchyme and their potential in cell sorting and tissue formation processes in the body are discussed.

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“…In vitro, the FH2 domain nucleates actin filaments from monomers Sagot et al, 2002b;Kovar et al, 2003;Li and Higgs, 2003;Harris et al, 2004;Kobielak et al, 2004), but distinct from other nucleators, it remains associated with the growing barbed end to promote elongation, even in the presence of barbed-end capping proteins Kovar et al, 2003;Li and Higgs, 2003;Pring et al, 2003;Harris et al, 2004;Kobielak et al, 2004;Moseley et al, 2004). The FH1 region is a proline-rich stretch that recruits profilin, an actin-monomer binding protein essential for formin function in vivo , to participate in FH2-mediated nucleation in vitro (Sagot et al, 2002b;Kovar et al, 2003;Pring et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Stable and Dynamic Axes of Polarity Use Distinct Formin Isoforms in Budding Yeast

Pruyne

Gao

et al. 2004

MBoC

151

208

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Bud growth in yeast is guided by myosin-driven delivery of secretory vesicles from the mother cell to the bud. We find transport occurs along two sets of actin cables assembled by two formin isoforms. The Bnr1p formin assembles cables that radiate from the bud neck into the mother, providing a stable mother-bud axis. These cables also depend on septins at the neck and are required for efficient transport from the mother to the bud. The Bni1p formin assembles cables that line the bud cortex and target vesicles to varying locations in the bud. Loss of these cables results in morphological defects as vesicles accumulate at the neck. Assembly of these cables depends on continued polarized secretion, suggesting vesicular transport provides a positive feedback signal for Bni1p activation, possibly by rho-proteins. By coupling different formin isoforms to unique cortical landmarks, yeast uses common cytoskeletal elements to maintain stable and dynamic axes in the same cell. INTRODUCTIONProper cell polarization requires a balance between dynamism and stability. Persistent systems, such as the apical and basolateral domains of epithelial cells, show a higher stability than flexible systems, such as cells undergoing chemotaxis. However, both types can use similar cytoskeletal components, so an important task in understanding the control of polarity is to identify features that influence persistence, and how those features integrate with the core cytoskeletal machinery providing the physical expression of polarity.The process of bud growth of the yeast Saccharomyces cerevisiae provides a model for examining the control of polarity (for reviews, see Bretscher, 2003;Chang and Peter, 2003). Secretory organelles, such as the Golgi and endoplasmic reticulum, are distributed throughout the bud and mother cell, whereas post-Golgi secretory vesicles concentrate at discrete growth sites at the cell cortex. These vesicles are guided to these sites along what are essentially two axes of polarity: a stable axis directing traffic from the mother into the bud, and a dynamic axis that fine-tunes delivery from the bud neck to specific regions in the bud, sending vesicles first to the small bud tip, then to the entire bud surface, and finally back toward the neck during mother/daughter separation. On delivery to these locations, post-Golgi vesicles fuse with the cell surface to promote localized cell expansion.Two class-V myosins, with heavy chains encoded by MYO2 (Johnston et al., 1991) and MYO4 (Haarer et al., 1994), propel cellular components, including vesicles, organelles, mRNAs, and microtubules, from the mother into the bud during growth and organelle segregation. The myosins move along cables of actin filaments that radiate throughout the cell in arrays oriented toward growth sites (Adams and Pringle, 1984;Kilmartin and Adams, 1984).Assembly of these cables depends on two formin homologues, Bni1p and Bnr1p (Evangelista et al., 2002;Sagot et al., 2002a), members of a family of cytoskeletal regulatory proteins defined by conserved fo...

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Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables

Abstract: Reference: de Joussineau, C., et al. 2003. Nature. 426:555-559. Filopodia allow epithelia to communicate over long distances. Alexandre/Macmillan

Cited by 347 publications

References 51 publications

Changes in E-cadherin rigidity sensing regulate cell adhesion

Changes in E-cadherin rigidity sensing regulate cell adhesion

Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells

Stable and Dynamic Axes of Polarity Use Distinct Formin Isoforms in Budding Yeast

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