scholarly journals Inside-out regulation of E-cadherin conformation and adhesion

2021 ◽  
Vol 118 (30) ◽  
pp. e2104090118
Author(s):  
Ramesh Koirala ◽  
Andrew Vae Priest ◽  
Chi-Fu Yen ◽  
Joleen S. Cheah ◽  
Willem-Jan Pannekoek ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Single Molecule ◽  
Myosin Ii ◽  
Actin Binding ◽  
Adhesive Properties ◽  
Single Molecule Level ◽  
Cytoskeletal Tension ◽  
Cell Adhesion Proteins ◽  
Inside Out ◽  
Cell Cell

Cadherin cell–cell adhesion proteins play key roles in tissue morphogenesis and wound healing. Cadherin ectodomains bind in two conformations, X-dimers and strand-swap dimers, with different adhesive properties. However, the mechanisms by which cells regulate ectodomain conformation are unknown. Cadherin intracellular regions associate with several actin-binding proteins including vinculin, which are believed to tune cell–cell adhesion by remodeling the actin cytoskeleton. Here, we show at the single-molecule level, that vinculin association with the cadherin cytoplasmic region allosterically converts weak X-dimers into strong strand-swap dimers and that this process is mediated by myosin II–dependent changes in cytoskeletal tension. We also show that in epithelial cells, ∼70% of apical cadherins exist as strand-swap dimers while the remaining form X-dimers, providing two cadherin pools with different adhesive properties. Our results demonstrate the inside-out regulation of cadherin conformation and establish a mechanistic role for vinculin in this process.

scholarly journals Inside-out regulation of E-cadherin conformation and adhesion

2020 ◽  
Author(s):  
Ramesh Koirala ◽  
Andrew Vae Priest ◽  
Chi-Fu Yen ◽  
Joleen S. Cheah ◽  
Martijn Gloerich ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Adhesion ◽  
Single Molecule ◽  
Allosteric Modulation ◽  
Actin Binding ◽  
Adhesive Properties ◽  
Single Molecule Level ◽  
Cell Adhesion Proteins ◽  
Inside Out ◽  
Cell Cell

ABSTRACTCadherin cell-cell adhesion proteins play key roles in tissue morphogenesis and wound healing. Cadherin ectodomains bind in two conformations, X-dimers and strand-swap dimers, with different adhesive properties. However, the mechanisms by which cells regulate ectodomain conformation are unknown. Cadherin intracellular regions associate with several actin-binding proteins including vinculin, which are believed to tune cell-cell adhesion, solely by remodeling the actin cytoskeleton. Here, we demonstrate that vinculin association with the cadherin cytoplasmic region, also allosterically regulates ectodomain structure and adhesion, by converting weaker X-dimers into stronger strand-swap dimers. We also show that in epithelial cells, only half of apical cadherins are linked to the cytoskeleton. Furthermore, only 70% of apical cadherins form strand-swap dimers while the remaining form X-dimers, which provides cells with two cadherin pools with different adhesive properties. Our results showing allosteric modulation of adhesion at the single-molecule level are the first demonstration of inside-out regulation of cadherin conformation.

scholarly journals The Small GTPase Rap1b: A Bidirectional Regulator of Platelet Adhesion Receptors

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Gianni Francesco Guidetti ◽  
Mauro Torti
Keyword(s):  
Cell Adhesion ◽  
Signaling Pathways ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Complex Pattern ◽  
Adhesive Properties ◽  
Adhesion Receptors ◽  
Inside Out

Integrins and other families of cell adhesion receptors are responsible for platelet adhesion and aggregation, which are essential steps for physiological haemostasis, as well as for the development of thrombosis. The modulation of platelet adhesive properties is the result of a complex pattern of inside-out and outside-in signaling pathways, in which the members of the Rap family of small GTPases are bidirectionally involved. This paper focuses on the regulation of the main Rap GTPase expressed in circulating platelets, Rap1b, downstream of adhesion receptors, and summarizes the most recent achievements in the investigation of the function of this protein as regulator of platelet adhesion and thrombus formation.

Molecular Motors: Force and Movement Generated by Single Myosin II Molecules

Physiology ◽  
2002 ◽  
Vol 17 (5) ◽  
pp. 213-218 ◽  
Author(s):  
Caspar Rüegg ◽  
Claudia Veigel ◽  
Justin E. Molloy ◽  
Stephan Schmitz ◽  
John C. Sparrow ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Myosin Ii ◽  
Force Production ◽  
Myosin Isoforms ◽  
Single Molecule Level ◽  
Recent Developments ◽  
Muscle Myosin

Muscle myosin II is an ATP-driven, actin-based molecular motor. Recent developments in optical tweezers technology have made it possible to study movement and force production on the single-molecule level and to find out how different myosin isoforms may have adapted to their specific physiological roles.

scholarly journals Dynamics of Tpm1.8 domains on actin filaments with single molecule resolution

2020 ◽  
Author(s):  
Ilina Bareja ◽  
Hugo Wioland ◽  
Miro Janco ◽  
Philip R. Nicovich ◽  
Antoine Jégou ◽  
...  
Keyword(s):  
Actin Filament ◽  
Single Molecule ◽  
Actin Filaments ◽  
High Probability ◽  
Actin Binding ◽  
Single Molecule Level ◽  
Filament Dynamics ◽  
Kinetics Of ◽  
Insight Into

ABSTRACTTropomyosins regulate dynamics and functions of the actin cytoskeleton by forming long chains along the two strands of actin filaments that act as gatekeepers for the binding of other actin-binding proteins. The fundamental molecular interactions underlying the binding of tropomyosin to actin are still poorly understood. Using microfluidics and fluorescence microscopy, we observed the binding of fluorescently labelled tropomyosin isoform Tpm1.8 to unlabelled actin filaments in real time. This approach in conjunction with mathematical modeling enabled us to quantify the nucleation, assembly and disassembly kinetics of Tpm1.8 on single filaments and at the single molecule level. Our analysis suggests that Tpm1.8 decorates the two strands of the actin filament independently. Nucleation of a growing tropomyosin domain proceeds with high probability as soon as the first Tpm1.8 molecule is stabilised by the addition of a second molecule, ultimately leading to full decoration of the actin filament. In addition, Tpm1.8 domains are asymmetrical, with enhanced dynamics at the edge oriented towards the barbed end of the actin filament. The complete description of Tpm1.8 kinetics on actin filaments presented here provides molecular insight into actin-tropomyosin filament formation and the role of tropomyosins in regulating actin filament dynamics.

scholarly journals Cell–Cell Adhesion Prevents Mutant Cells Lacking Myosin II from Penetrating Aggregation Streams ofDictyostelium

1996 ◽  
Vol 175 (2) ◽  
pp. 218-226 ◽  
Author(s):  
Xiaoxin Susan Xu ◽  
Adam Kuspa ◽  
Danny Fuller ◽  
William F. Loomis ◽  
David A. Knecht
Keyword(s):  
Cell Adhesion ◽  
Myosin Ii ◽  
Mutant Cells ◽  
Cell Cell

scholarly journals Tetraspanin CD151 maintains vascular stability by balancing the forces of cell adhesion and cytoskeletal tension

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4274-4284 ◽  
Author(s):  
Feng Zhang ◽  
Jarett E. Michaelson ◽  
Simon Moshiach ◽  
Norman Sachs ◽  
Wenyuan Zhao ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Cell Matrix ◽  
Vascular Morphogenesis ◽  
Vascular Stability ◽  
Optimal Functions ◽  
Cytoskeletal Tension ◽  
Cell Cell

Abstract Tetraspanin CD151 is highly expressed in endothelial cells and regulates pathologic angiogenesis. However, the mechanism by which CD151 promotes vascular morphogenesis and whether CD151 engages other vascular functions are unclear. Here we report that CD151 is required for maintaining endothelial capillary-like structures formed in vitro and the integrity of endothelial cell-cell and cell-matrix contacts in vivo. In addition, vascular permeability is markedly enhanced in the absence of CD151. As a global regulator of endothelial cell-cell and cell-matrix adhesions, CD151 is needed for the optimal functions of various cell adhesion proteins. The loss of CD151 elevates actin cytoskeletal traction by up-regulating RhoA signaling and diminishes actin cortical meshwork by down-regulating Rac1 activity. The inhibition of RhoA or activation of cAMP signaling stabilizes CD151-silenced or -null endothelial structure in vascular morphogenesis. Together, our data demonstrate that CD151 maintains vascular stability by promoting endothelial cell adhesions, especially cell-cell adhesion, and confining cytoskeletal tension.

scholarly journals α-Catenin-independent Recruitment of ZO-1 to Nectin-based Cell-Cell Adhesion Sites through Afadin

2001 ◽  
Vol 12 (6) ◽  
pp. 1595-1609 ◽  
Author(s):  
Shigekazu Yokoyama ◽  
Kouichi Tachibana ◽  
Hiroyuki Nakanishi ◽  
Yasunori Yamamoto ◽  
Kenji Irie ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Tight Junctions ◽  
Cell Lines ◽  
Adhesion Molecule ◽  
Binding Protein ◽  
Actin Binding ◽  
Actin Binding Protein ◽  
Adhesion Sites ◽  
Cell Cell

ZO-1 is an actin filament (F-actin)–binding protein that localizes to tight junctions and connects claudin to the actin cytoskeleton in epithelial cells. In nonepithelial cells that have no tight junctions, ZO-1 localizes to adherens junctions (AJs) and may connect cadherin to the actin cytoskeleton indirectly through β- and α-catenins as one of many F-actin–binding proteins. Nectin is an immunoglobulin-like adhesion molecule that localizes to AJs and is associated with the actin cytoskeleton through afadin, an F-actin–binding protein. Ponsin is an afadin- and vinculin-binding protein that also localizes to AJs. The nectin-afadin complex has a potency to recruit the E-cadherin–β-catenin complex through α-catenin in a manner independent of ponsin. By the use of cadherin-deficient L cell lines stably expressing various components of the cadherin-catenin and nectin-afadin systems, and α-catenin–deficient F9 cell lines, we examined here whether nectin recruits ZO-1 to nectin-based cell-cell adhesion sites. Nectin showed a potency to recruit not only α-catenin but also ZO-1 to nectin-based cell-cell adhesion sites. This recruitment of ZO-1 was dependent on afadin but independent of α-catenin and ponsin. These results indicate that ZO-1 localizes to cadherin-based AJs through interactions not only with α-catenin but also with the nectin-afadin system.

scholarly journals LI-Cadherin–mediated Cell–Cell Adhesion Does Not Require Cytoplasmic Interactions

1997 ◽  
Vol 136 (5) ◽  
pp. 1109-1121 ◽  
Author(s):  
Bertolt Kreft ◽  
Dietmar Berndorff ◽  
Anja Böttinger ◽  
Silvia Finnemann ◽  
Doris Wedlich ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Adhesive Properties ◽  
Glycosyl Phosphatidylinositol ◽  
Cytoplasmic Proteins ◽  
Classical Cadherins ◽  
Drosophila S2 Cells ◽  
Detergent Extraction ◽  
Dependent Cell ◽  
Cell Cell

The adhesive function of classical cadherins depends on the association with cytoplasmic proteins, termed catenins, which serve as a link between cadherins and the actin cytoskeleton. LI-cadherin, a structurally different member of the cadherin family, mediates Ca2+-dependent cell–cell adhesion, although its markedly short cytoplasmic domain exhibits no homology to this highly conserved region of classical cadherins. We now examined whether the adhesive function of LI-cadherin depends on the interaction with catenins, the actin cytoskeleton or other cytoplasmic components. In contrast to classical cadherins, LI-cadherin, when expressed in mouse L cells, was neither associated with catenins nor did it induce an upregulation of β-catenin. Consistent with these findings, LI-cadherin was not resistant to detergent extraction and did not induce a reorganization of the actin cytoskeleton. However, LI-cadherin was still able to mediate Ca2+dependent cell–cell adhesion. To analyze whether this function requires any interaction with proteins other than catenins, a glycosyl phosphatidylinositol–anchored form of LI-cadherin (LI-cadherinGPI) was constructed and expressed in Drosophila S2 cells. The mutant protein was able to induce Ca2+-dependent, homophilic cell–cell adhesion, and its adhesive properties were indistinguishable from those of wild type LI-cadherin. These findings indicate that the adhesive function of LI-cadherin is independent of any interaction with cytoplasmic components, and consequently should not be sensitive to regulatory mechanisms affecting the binding of classical cadherins to catenins and to the cytoskeleton. Thus, we postulate that the adhesive function of LI-cadherin is complementary to that of coexpressed classical cadherins ensuring cell–cell contacts even under conditions that downregulate the function of classical cadherins.

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