scholarly journals Rap1: a key regulator in cell-cell junction formation

2006 ◽  
Vol 120 (1) ◽  
pp. 17-22 ◽  
Author(s):  
M. R. H. Kooistra ◽  
N. Dube ◽  
J. L. Bos
Keyword(s):  
Cell Junction ◽  
Junction Formation ◽  
Cell Cell

scholarly journals PLEKHG4B enables actin cytoskeletal remodeling during epithelial cell-cell junction formation

2020 ◽  
pp. jcs.249078
Author(s):  
Komaki Ninomiya ◽  
Kai Ohta ◽  
Kazunari Yamashita ◽  
Kensaku Mizuno ◽  
Kazumasa Ohashi
Keyword(s):  
Epithelial Cell ◽  
A549 Cells ◽  
Cell Junctions ◽  
Cell Junction ◽  
Nucleotide Exchange ◽  
Actin Bundles ◽  
Rhoa Activity ◽  
Cytoskeletal Remodeling ◽  
Junction Formation ◽  
Cell Cell

Cell-cell junction formation requires actin cytoskeletal remodeling. Here we show that PLEKHG4B, a Rho-guanine nucleotide exchange factor (Rho-GEF), plays a crucial role in epithelial cell-cell junction formation. Knockdown of PLEKHG4B decreased Cdc42 activity and tended to increase RhoA activity in A549 cells. A549 monolayer cells showed 'closed junctions' with closely packed actin bundles along the cell-cell contacts, but PLEKHG4B knockdown suppressed closed junction formation and exhibited 'open junctions' with split actin bundles located away from the cell-cell boundary. In calcium-switch assays, PLEKHG4B knockdown delayed the conversion of open junctions to closed junctions and β-catenin accumulation at cell-cell junctions. Further, PLEKHG4B knockdown abrogated the reduction in myosin activity normally seen in the later stage of junction formation. The aberrant myosin activation and impairments in closed junction formation in PLEKHG4B-knockdown cells were reverted by ROCK inhibition or LARG/PDZ-RhoGEF knockdown. These results suggest that PLEKHG4B enables actin remodeling during epithelial cell-cell junction maturation, probably by reducing myosin activity in the later stage of junction formation, through suppressing LARG/PDZ-RhoGEF and RhoA-ROCK activities. We also showed that annexin-A2 participates in PLEKHG4B localization to cell-cell junctions.

scholarly journals The cytoskeletal mechanisms of cell–cell junction formation in endothelial cells

2012 ◽  
Vol 23 (2) ◽  
pp. 310-323 ◽  
Author(s):  
Matthew K. Hoelzle ◽  
Tatyana Svitkina
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Adherens Junctions ◽  
Myosin Ii ◽  
Vital Role ◽  
Cell Junction ◽  
Bridge Formation ◽  
Actin Organization ◽  
Junction Formation ◽  
Cell Cell

The actin cytoskeleton and associated proteins play a vital role in cell–cell adhesion. However, the procedure by which cells establish adherens junctions remains unclear. We investigated the dynamics of cell–cell junction formation and the corresponding architecture of the underlying cytoskeleton in cultured human umbilical vein endothelial cells. We show that the initial interaction between cells is mediated by protruding lamellipodia. On their retraction, cells maintain contact through thin bridges formed by filopodia-like protrusions connected by VE-cadherin–rich junctions. Bridges share multiple features with conventional filopodia, such as an internal actin bundle associated with fascin along the length and vasodilator-stimulated phosphoprotein at the tip. It is striking that, unlike conventional filopodia, transformation of actin organization from the lamellipodial network to filopodial bundle during bridge formation occurs in a proximal-to-distal direction and is accompanied by recruitment of fascin in the same direction. Subsequently, bridge bundles recruit nonmuscle myosin II and mature into stress fibers. Myosin II activity is important for bridge formation and accumulation of VE-cadherin in nascent adherens junctions. Our data reveal a mechanism of cell–cell junction formation in endothelial cells using lamellipodia as the initial protrusive contact, subsequently transforming into filopodia-like bridges connected through adherens junctions. Moreover, a novel lamellipodia-to-filopodia transition is used in this context.

scholarly journals Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex

2012 ◽  
Vol 198 (4) ◽  
pp. 677-693 ◽  
Author(s):  
Ahmed Elbediwy ◽  
Ceniz Zihni ◽  
Stephen J. Terry ◽  
Peter Clark ◽  
Karl Matter ◽  
...  
Keyword(s):  
Dynamic Control ◽  
Scaffolding Protein ◽  
Cell Junction ◽  
Membrane Remodeling ◽  
Filamentous Actin ◽  
Capping Protein ◽  
Junction Formation ◽  
Guanosine Triphosphatase ◽  
Epithelial Junction ◽  
Cell Cell

Epithelial cell–cell adhesion and morphogenesis require dynamic control of actin-driven membrane remodeling. The Rho guanosine triphosphatase (GTPase) Cdc42 regulates sequential molecular processes during cell–cell junction formation; hence, mechanisms must exist that inactivate Cdc42 in a temporally and spatially controlled manner. In this paper, we identify SH3BP1, a GTPase-activating protein for Cdc42 and Rac, as a regulator of junction assembly and epithelial morphogenesis using a functional small interfering ribonucleic acid screen. Depletion of SH3BP1 resulted in loss of spatial control of Cdc42 activity, stalled membrane remodeling, and enhanced growth of filopodia. SH3BP1 formed a complex with JACOP/paracingulin, a junctional adaptor, and CD2AP, a scaffolding protein; both were required for normal Cdc42 signaling and junction formation. The filamentous actin–capping protein CapZ also associated with the SH3BP1 complex and was required for control of actin remodeling. Epithelial junction formation and morphogenesis thus require a dual activity complex, containing SH3BP1 and CapZ, that is recruited to sites of active membrane remodeling to guide Cdc42 signaling and cytoskeletal dynamics.

scholarly journals Accumulation of a microtubule-binding protein, pp170, at desmosomal plaques

1992 ◽  
Vol 117 (4) ◽  
pp. 813-824 ◽  
Author(s):  
IU Wacker ◽  
JE Rickard ◽  
JR De Mey ◽  
TE Kreis
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Mdck Cells ◽  
Binding Protein ◽  
Cell Junction ◽  
Microtubule Binding ◽  
Epithelial Cell Polarity ◽  
Junction Formation ◽  
Cell Cell

The establishment of epithelial cell polarity correlates with the formation of specialized cell-cell junctions and striking changes in the organization of microtubules. A significant fraction of the microtubules in MDCK cells become stabilized, noncentrosomally organized, and arranged in longitudinal bundles in the apical-basal axis. This correlation suggests a functional link between cell-cell junction formation and control of microtubule organization. We have followed the distribution of pp170, a recently described microtubule-binding protein, during establishment of epithelial cell polarity. This protein shows the typical patchy distribution along microtubules in subconfluent fibroblasts and epithelial cells, often associated with the peripheral ends of a subpopulation of microtubules. In contrast to its localization in confluent fibroblasts (A72) and HeLa cells, however, pp170 accumulates in patches delineating the regions of cell-cell contacts in confluent polarizing epithelial cells (MDCK and Caco-2). Double immunolocalization with antibodies specific for cell-cell junction proteins, confocal microscopy, and immunoelectron microscopy on polarized MDCK cells suggest that pp170 accumulates at desmosomal plaques. Furthermore, microtubules and desmosomes are found in close contact. Maintenance of the desmosomal association of pp170 is dependent on intact microtubules in 3-d-old, but not in 1-d-old MDCK cell cultures. This suggests a regulated interaction between microtubules and desmosomes and a role for pp170 in the control of changes in the properties of microtubules induced by epithelial cell-cell junction formation.

scholarly journals Golgi-associated cPLA2α Regulates Endothelial Cell–Cell Junction Integrity by Controlling the Trafficking of Transmembrane Junction Proteins

2009 ◽  
Vol 20 (19) ◽  
pp. 4225-4234 ◽  
Author(s):  
Elsa Regan-Klapisz ◽  
Vincent Krouwer ◽  
Miriam Langelaar-Makkinje ◽  
Laxman Nallan ◽  
Michael Gelb ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Intracellular Trafficking ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Cell Junction ◽  
Tight Junction Formation ◽  
Junction Formation ◽  
Junction Proteins ◽  
Cell Cell

In endothelial cells specifically, cPLA2α translocates from the cytoplasm to the Golgi complex in response to cell confluence. Considering the link between confluence and cell–cell junction formation, and the emerging role of cPLA2α in intracellular trafficking, we tested whether Golgi-associated cPLA2α is involved in the trafficking of junction proteins. Here, we show that the redistribution of cPLA2α from the cytoplasm to the Golgi correlates with adherens junction maturation and occurs before tight junction formation. Disruption of adherens junctions using a blocking anti-VE-cadherin antibody reverses the association of cPLA2α with the Golgi. Silencing of cPLA2α and inhibition of cPLA2α enzymatic activity using various inhibitors result in the diminished presence of the transmembrane junction proteins VE-cadherin, occludin, and claudin-5 at cell–cell contacts, and in their accumulation at the Golgi. Altogether, our data support the idea that VE-cadherin triggers the relocation of cPLA2α to the Golgi and that in turn, Golgi-associated cPLA2α regulates the transport of transmembrane junction proteins through or from the Golgi, thereby controlling the integrity of endothelial cell–cell junctions.

How cells tell up from down and stick together to construct multicellular tissues – interplay between apicobasal polarity and cell–cell adhesion

2021 ◽  
Vol 134 (21) ◽  
Author(s):  
Claudia G. Vasquez ◽  
Eva L. de la Serna ◽  
Alexander R. Dunn
Keyword(s):  
Cell Adhesion ◽  
Protein Complexes ◽  
Basic Function ◽  
Cell Junction ◽  
Evolutionary Innovation ◽  
Apicobasal Polarity ◽  
Complex Architectures ◽  
Main Components ◽  
Definition Of ◽  
Cell Cell

ABSTRACT Polarized epithelia define a topological inside and outside, and hence constitute a key evolutionary innovation that enabled the construction of complex multicellular animal life. Over time, this basic function has been elaborated upon to yield the complex architectures of many of the organs that make up the human body. The two processes necessary to yield a polarized epithelium, namely regulated adhesion between cells and the definition of the apicobasal (top–bottom) axis, have likewise undergone extensive evolutionary elaboration, resulting in multiple sophisticated protein complexes that contribute to both functions. Understanding how these components function in combination to yield the basic architecture of a polarized cell–cell junction remains a major challenge. In this Review, we introduce the main components of apicobasal polarity and cell–cell adhesion complexes, and outline what is known about their regulation and assembly in epithelia. In addition, we highlight studies that investigate the interdependence between these two networks. We conclude with an overview of strategies to address the largest and arguably most fundamental unresolved question in the field, namely how a polarized junction arises as the sum of its molecular parts.

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