scholarly journals Tyrosine-based Signals Regulate the assembly of Daple•PARD3 Complex at Cell-cell Junctions during Polarized Planar Cell Migration

2019 ◽  
Author(s):  
Jason Ear ◽  
Anokhi Saklecha ◽  
Navin Rajapakse ◽  
Julie Choi ◽  
Majid Ghassemian ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tyrosine Kinases ◽  
Planar Cell Polarity ◽  
Pdz Domain ◽  
Cell Junctions ◽  
Cell Contact ◽  
Binding Motif ◽  
Planar Polarity ◽  
Gradient Sensing ◽  
Cell Cell

SummaryPolarized distribution of organelles and molecules inside a cell is vital for a range of cellular processes and its loss is frequently encountered in disease. Polarization during planar cell migration is a special condition in which cellular orientation is triggered by cell-cell contact. Here, we demonstrate that the multi-modular signaling scaffold Daple (CCDC88C) is a component of cell junctions in epithelial cells which serves like a cellular ‘compass’ for establishing and maintaining contact-triggered planar polarity via its interaction with the polarity regulator PARD3, which has been implicated in both apical-basal and planar polarity. This interaction, mediated by Daple’s PDZ-binding motif (PBM) and the third PDZ domain of PARD3, is fine-tuned by two tyrosine phosphoevents on Daple’s PBM that are known to be triggered by a multitude of receptor and non-receptor tyrosine kinases, such as Src. Hypophosphorylation strengthens the interaction, whereas hyperphosphorylation disrupts it. These findings reveal an unexpected role of Daple within the planar cell polarity pathway as a platform for signal integration and gradient sensing for tyrosine-based signals.

scholarly journals Association of ARVCF with Zonula Occludens (ZO)-1 and ZO-2: Binding to PDZ-Domain Proteins and Cell-Cell Adhesion Regulate Plasma Membrane and Nuclear Localization of ARVCF

2004 ◽  
Vol 15 (12) ◽  
pp. 5503-5515 ◽  
Author(s):  
P. Jaya Kausalya ◽  
Dominic C.Y. Phua ◽  
Walter Hunziker
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Nuclear Localization ◽  
Pdz Domain ◽  
Cell Contact ◽  
Binding Motif ◽  
Zonula Occludens ◽  
Pdz Domain Proteins ◽  
E Cadherin ◽  
Cell Cell

ARVCF, an armadillo-repeat protein of the p120ctnfamily, associates with classical cadherins and is present in adherens junctions, but its function is poorly understood. Here, we show that ARVCF interacts via a C-terminal PDZ-binding motif with zonula occludens (ZO)-1 and ZO-2. ARVCF and ZO-1 partially colocalize in the vicinity of the apical adhesion complex in polarized epithelial Madin-Darby canine kidney cells. ARVCF, ZO-1, and E-cadherin form a complex and are recruited to sites of initial cell-cell contact in sparse cell cultures. E-cadherin binding and plasma membrane localization of ARVCF require the PDZ-binding motif. Disruption of cell-cell adhesion releases ARVCF from the plasma membrane and an increased fraction of the protein localizes to the nucleus. Nuclear localization of ARVCF also requires the PDZ-binding motif and can be mediated by the PDZ domains of ZO-2. Thus, the interaction of ARVCF with distinct PDZ-domain proteins determines its subcellular localization. Interactions with ZO-1 and ZO-2, in particular, may mediate recruitment of ARVCF to the plasma membrane and the nucleus, respectively, possibly in response to cell-cell adhesion cues.

scholarly journals The Junction-associated Protein AF-6 Interacts and Clusters with Specific Eph Receptor Tyrosine Kinases at Specialized Sites of Cell–Cell Contact in the Brain

1999 ◽  
Vol 144 (2) ◽  
pp. 361-371 ◽  
Author(s):  
Michael Buchert ◽  
Stefan Schneider ◽  
Virginia Meskenaite ◽  
Mark T. Adams ◽  
Eli Canaani ◽  
...  
Keyword(s):  
Rat Brain ◽  
Fluorescent Protein ◽  
Pdz Domain ◽  
Cell Junctions ◽  
Cell Contact ◽  
Physical Interaction ◽  
Eph Receptors ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Cell Cell

The AF-6/afadin protein, which contains a single PDZ domain, forms a peripheral component of cell membranes at specialized sites of cell–cell junctions. To identify potential receptor-binding targets of AF-6 we screened the PDZ domain of AF-6 against a range of COOH-terminal peptides selected from receptors having potential PDZ domain-binding termini. The PDZ domain of AF-6 interacts with a subset of members of the Eph subfamily of RTKs via its COOH terminus both in vitro and in vivo. Cotransfection of a green fluorescent protein-tagged AF-6 fusion protein with full-length Eph receptors into heterologous cells induces a clustering of the Eph receptors and AF-6 at sites of cell–cell contact. Immunohistochemical analysis in the adult rat brain reveals coclustering of AF-6 with Eph receptors at postsynaptic membrane sites of excitatory synapses in the hippocampus. Furthermore, AF-6 is a substrate for a subgroup of Eph receptors and phosphorylation of AF-6 is dependent on a functional kinase domain of the receptor. The physical interaction of endogenous AF-6 with Eph receptors is demonstrated by coimmunoprecipitation from whole rat brain lysates. AF-6 is a candidate for mediating the clustering of Eph receptors at postsynaptic specializations in the adult rat brain.

scholarly journals The Ras Target AF-6 Interacts with ZO-1 and Serves as a Peripheral Component of Tight Junctions in Epithelial Cells

1997 ◽  
Vol 139 (3) ◽  
pp. 785-795 ◽  
Author(s):  
Takaharu Yamamoto ◽  
Naozumi Harada ◽  
Kyoko Kano ◽  
Shin-ichiro Taya ◽  
Eli Canaani ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Adherens Junctions ◽  
Pdz Domain ◽  
Cell Junctions ◽  
Cell Contact ◽  
Fusion Partner ◽  
Cell Contacts ◽  
Contact Sites ◽  
Cell Cell

The dynamic rearrangement of cell–cell junctions such as tight junctions and adherens junctions is a critical step in various cellular processes, including establishment of epithelial cell polarity and developmental patterning. Tight junctions are mediated by molecules such as occludin and its associated ZO-1 and ZO-2, and adherens junctions are mediated by adhesion molecules such as cadherin and its associated catenins. The transformation of epithelial cells by activated Ras results in the perturbation of cell–cell contacts. We previously identified the ALL-1 fusion partner from chromosome 6 (AF-6) as a Ras target. AF-6 has the PDZ domain, which is thought to localize AF-6 at the specialized sites of plasma membranes such as cell–cell contact sites. We investigated roles of Ras and AF-6 in the regulation of cell–cell contacts and found that AF-6 accumulated at the cell–cell contact sites of polarized MDCKII epithelial cells and had a distribution similar to that of ZO-1 but somewhat different from those of catenins. Immunoelectron microscopy revealed a close association between AF-6 and ZO-1 at the tight junctions of MDCKII cells. Native and recombinant AF-6 interacted with ZO-1 in vitro. ZO-1 interacted with the Ras-binding domain of AF-6, and this interaction was inhibited by activated Ras. AF-6 accumulated with ZO-1 at the cell–cell contact sites in cells lacking tight junctions such as Rat1 fibroblasts and PC12 rat pheochromocytoma cells. The overexpression of activated Ras in Rat1 cells resulted in the perturbation of cell–cell contacts, followed by a decrease of the accumulation of AF-6 and ZO-1 at the cell surface. These results indicate that AF-6 serves as one of the peripheral components of tight junctions in epithelial cells and cell–cell adhesions in nonepithelial cells, and that AF-6 may participate in the regulation of cell–cell contacts, including tight junctions, via direct interaction with ZO-1 downstream of Ras.

scholarly journals Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 135
Author(s):  
Pau Urdeitx ◽  
Mohamed H. Doweidar
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Computational Models ◽  
Cell Junctions ◽  
Tissue Formation ◽  
Cardiac Muscle Cells ◽  
Cell Processes ◽  
Electrical Stimuli ◽  
Cell Cell

Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In addition, active and reciprocal cell–cell and cell–extracellular matrix interactions are essential to be considered during formation of complex tissue such as myocardial tissue. In this sense, computational models can offer new perspectives and key information on the cell microenvironment. Thus, we present a new computational 3D model, based on the Finite Element Method, where a complex extracellular matrix with piezoelectric properties interacts with cardiac muscle cells during the first steps of tissue formation. This model includes collective behavior and cell processes such as cell migration, maturation, differentiation, proliferation, and apoptosis. The model has employed to study the initial stages of in vitro cardiac aggregate formation, considering cell–cell junctions, under different extracellular matrix configurations. Three different cases have been purposed to evaluate cell behavior in fibered, mechanically stimulated fibered, and mechanically stimulated piezoelectric fibered extra-cellular matrix. In this last case, the cells are guided by the coupling of mechanical and electrical stimuli. Accordingly, the obtained results show the formation of more elongated groups and enhancement in cell proliferation.

scholarly journals Myosin 1e is a component of the glomerular slit diaphragm complex that regulates actin reorganization during cell-cell contact formation in podocytes

2013 ◽  
Vol 305 (4) ◽  
pp. F532-F544 ◽  
Author(s):  
J. Bi ◽  
S. E. Chase ◽  
C. D. Pellenz ◽  
H. Kurihara ◽  
A. S. Fanning ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Molecular Motor ◽  
Subcellular Fractionation ◽  
Slit Diaphragm ◽  
Cell Junctions ◽  
Cell Contact ◽  
Filtration Barrier ◽  
Renal Glomeruli ◽  
Actin Cables ◽  
Cell Cell

Glomerular visceral epithelial cells, also known as podocytes, are critical to both normal kidney function and the development of kidney disease. Podocyte actin cytoskeleton and their highly specialized cell-cell junctions (also called slit diaphragm complexes) play key roles in controlling glomerular filtration. Myosin 1e (myo1e) is an actin-based molecular motor that is expressed in renal glomeruli. Disruption of the Myo1e gene in mice and humans promotes podocyte injury and results in the loss of the integrity of the glomerular filtration barrier. Here, we have used biochemical and microscopic approaches to determine whether myo1e is associated with the slit diaphragm complexes in glomerular podocytes. Myo1e was consistently enriched in the slit diaphragm fraction during subcellular fractionation of renal glomeruli and colocalized with the slit diaphragm markers in mouse kidney. Live cell imaging studies showed that myo1e was recruited to the newly formed cell-cell junctions in cultured podocytes, where it colocalized with the actin filament cables aligned with the nascent contacts. Myo1e-null podocytes expressing FSGS-associated myo1e mutant (A159P) did not efficiently assemble actin cables along new cell-cell junctions. We have mapped domains in myo1e that were critical for its localization to cell-cell junctions and determined that the SH3 domain of myo1e tail interacts with ZO-1, a component of the slit diaphragm complex and tight junctions. These findings suggest that myo1e represents a component of the slit diaphragm complex and may contribute to regulating junctional integrity in kidney podocytes.

scholarly journals N-Cadherin Association with Lipid Rafts Regulates Its Dynamic Assembly at Cell-Cell Junctions in C2C12 Myoblasts

2005 ◽  
Vol 16 (5) ◽  
pp. 2168-2180 ◽  
Author(s):  
Marie Causeret ◽  
Nicolas Taulet ◽  
Franck Comunale ◽  
Cyril Favard ◽  
Cécile Gauthier-Rouvière
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Cell Junctions ◽  
Cell Contact ◽  
C2c12 Myoblasts ◽  
Cell Contacts ◽  
Dynamic Assembly ◽  
Cell Cell

Cadherins are homophilic cell-cell adhesion molecules implicated in cell growth, differentiation, and organization into tissues during embryonic development. They accumulate at cell-cell contact sites and act as adhesion-activated signaling receptors. Here, we show that the dynamic assembly of N-cadherin at cell-cell contacts involves lipid rafts. In C2C12 myoblasts, immunofluorescence and biochemical experiments demonstrate that N-cadherin present at cell-cell contacts is colocalized with lipid rafts. Disruption of lipid rafts leads to the inhibition of cell-cell adhesion and disorganization of N-cadherin–dependent cell-cell contacts without modifying the association of N-cadherin with catenins and its availability at the plasma membrane. Fluorescent recovery after photobleaching experiments demonstrate that at the dorsal plasma membrane, lipid rafts are not directly involved in the diffusional mobility of N-cadherin. In contrast, at cell-cell junctions N-cadherin association with lipid rafts allows its stabilization enabling the formation of a functional adhesive complex. We show that lipid rafts, as homophilic interaction and F-actin association, stabilize cadherin-dependent adhesive complexes. Homophilic interactions and F-actin association of N-cadherin are both required for its association to lipid rafts. We thus identify lipid rafts as new regulators of cadherin-mediated cell adhesion.

scholarly journals Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis

2019 ◽  
Vol 116 (10) ◽  
pp. 4291-4296 ◽  
Author(s):  
Taihei Fujimori ◽  
Akihiko Nakajima ◽  
Nao Shimada ◽  
Satoshi Sawai
Keyword(s):  
Cell Migration ◽  
Cell Movement ◽  
Tissue Level ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Contact Activation ◽  
Membrane Recruitment ◽  
Cell Rearrangement ◽  
Cell Protrusion ◽  
Cell Cell

Despite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain largely undefined. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning; however, in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoebaDictyostelium discoideumwhere the organizing center or the “tip” self-organizes as a result of sorting of differentiating prestalk and prespore cells. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode ofDictyosteliumcell migration that is strictly directed by cell–cell contact. The cell–cell contact signal is mediated by E-set Ig-like domain-containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of the SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude toward the contact signal as well as to chemotax toward cAMP; however, when given both signals, prestalk cells orient toward the chemoattractant, whereas prespore cells choose the contact signal. These data suggest a model of cell sorting by competing juxtacrine and diffusive cues, each with potential to drive its own mode of collective cell migration.

scholarly journals Regulation of Endothelial Cell Motility by Complexes of Tetraspan Molecules CD81/TAPA-1 and CD151/PETA-3 with α3β1 Integrin Localized at Endothelial Lateral Junctions

1998 ◽  
Vol 141 (3) ◽  
pp. 791-804 ◽  
Author(s):  
María Yáñez-Mó ◽  
Arántzazu Alfranca ◽  
Carlos Cabañas ◽  
Mónica Marazuela ◽  
Reyes Tejedor ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Cell Motility ◽  
Cell Polarization ◽  
Cell Junctions ◽  
Cell Junction ◽  
Cell Contact ◽  
Collagen Gels ◽  
Α3β1 Integrin ◽  
Cell Cell

Cell-to-cell junction structures play a key role in cell growth rate control and cell polarization. In endothelial cells (EC), these structures are also involved in regulation of vascular permeability and leukocyte extravasation. To identify novel components in EC intercellular junctions, mAbs against these cells were produced and selected using a morphological screening by immunofluorescence microscopy. Two novel mAbs, LIA1/1 and VJ1/16, specifically recognized a 25-kD protein that was selectively localized at cell–cell junctions of EC, both in the primary formation of cell monolayers and when EC reorganized in the process of wound healing. This antigen corresponded to the recently cloned platelet-endothelial tetraspan antigen CD151/PETA-3 (platelet-endothelial tetraspan antigen-3), and was consistently detected at EC cell–cell contact sites. In addition to CD151/PETA-3, two other members of the tetraspan superfamily, CD9 and CD81/ TAPA-1 (target of antiproliferative antibody-1), localized at endothelial cell-to-cell junctions. Biochemical analysis demonstrated molecular associations among tetraspan molecules themselves and those of CD151/ PETA-3 and CD9 with α3β1 integrin. Interestingly, mAbs directed to both CD151/PETA-3 and CD81/ TAPA-1 as well as mAb specific for α3 integrin, were able to inhibit the migration of ECs in the process of wound healing. The engagement of CD151/PETA-3 and CD81/TAPA-1 inhibited the movement of individual ECs, as determined by quantitative time-lapse video microscopy studies. Furthermore, mAbs against the CD151/PETA-3 molecule diminished the rate of EC invasion into collagen gels. In addition, these mAbs were able to increase the adhesion of EC to extracellular matrix proteins. Together these results indicate that CD81/TAPA-1 and CD151/PETA-3 tetraspan molecules are components of the endothelial lateral junctions implicated in the regulation of cell motility, either directly or by modulation of the function of the associated integrin heterodimers.

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