Adherens junction: the ensemble of specialized cadherin clusters

Troyanovsky, Sergey M.

doi:10.1016/j.tcb.2022.08.007

Cited by 35 publications

(18 citation statements)

References 147 publications

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“…Together, these results suggest that members of that family of genes might be involved in promoting drug taking behaviors in the presence of foot-shock punishment. Cadherins are a family of transmembrane protein characterized by 5 CDH repeats that participate in calciumregulated interactions (Troyanovsky, 2022). These proteins also play important roles in synaptic changes involved in learning and memory via their interactions with beta-catenin (Bozdagi et al, 2000;Huber et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules

Munoz

Jayanthi²,

Ladenheim³

et al. 2023

Front. Mol. Neurosci.

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Methamphetamine (METH) is a popular but harmful psychostimulant. METH use disorder (MUD) is characterized by compulsive and continued use despite adverse life consequences. METH users experience impairments in learning and memory functions that are thought to be secondary to METH-induced abnormalities in the hippocampus. Recent studies have reported that about 50% of METH users develop MUD, suggesting that there may be differential molecular effects of METH between the brains of individuals who met criteria for addiction and those who did not after being exposed to the drug. The present study aimed at identifying potential transcriptional differences between compulsive and non-compulsive METH self-administering male rats by measuring global gene expression changes in the hippocampus using RNA sequencing. Herein, we used a model of METH self-administration (SA) accompanied by contingent foot-shock punishment. This approach led to the separation of animals into shock-resistant rats (compulsive) that continued to take METH and shock-sensitive rats (non-compulsive) that suppressed their METH intake in the presence of punished METH taking. Rats were euthanized 2 h after the last METH SA plus foot-shock session. Their hippocampi were immediately removed, frozen, and used later for RNA sequencing and qRT-PCR analyses. RNA sequencing analyses revealed differential expression of mRNAs encoding cell adhesion molecules (CAMs) between the two rat phenotypes. qRT-PCR analyses showed significant higher levels of Cdh1, Glycam1, and Mpzl2 mRNAs in the compulsive rats in comparison to non-compulsive rats. The present results implicate altered CAM expression in the hippocampus in the behavioral manifestations of continuous compulsive METH taking in the presence of adverse consequences. Our results raise the novel possibility that altered CAM expression might play a role in compulsive METH taking and the cognitive impairments observed in MUD patients.

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Section: Discussionmentioning

confidence: 99%

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules

Munoz

Jayanthi²,

Ladenheim³

et al. 2023

Front. Mol. Neurosci.

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“…This initially suggested a simple linear connection to actin, via the ability of alpha-catenin to bind actin. However, new data made this picture increasingly complex, with the addition of many additional proteins at the AJ:cytoskeletal interface and the realization that the structure and function of this multiprotein assemblage is altered by applied force, via mechanosensitive feedback loops (Yap et al ., 2018; Troyanovsky, 2022). Thus, evolution shaped an exceptionally robust multiprotein machine to accommodate force on AJs during the complex events of morphogenesis (Fernandez-Gonzalez and Peifer, 2022).…”

Section: Introductionmentioning

confidence: 99%

Polychaetoid/ZO-1 strengthens cell junctions under tension while localizing differently than core adherens junction proteins

Schmidt

Finegan

Häring

et al. 2023

Preprint

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During embryonic development dramatic cell shape changes and movements re-shape the embryonic body plan. These require robust but dynamic linkage between the cell-cell adherens junctions and the force-generating actomyosin cytoskeleton. Our view of this linkage has evolved, and we now realize linkage is mediated by a mechanosensitive multiprotein complex assembled via multivalent connections. Here we combine genetic, cell biological and modeling approaches to define the mechanism of action and functions of an important player,DrosophilaPolychaetoid, homolog of mammalian ZO-1. Our data reveal that Pyd reinforces cell junctions under elevated tension, and facilitates cell rearrangements. Pyd is important to maintain junctional contractility and in its absence cell rearrangements stall. We next use structured illumination microscopy to define the molecular architecture of cell-cell junctions during these events. The cadherin-catenin complex and Cno both localize to puncta along the junctional membrane, but are differentially enriched in different puncta. Pyd, in contrast, exhibits a distinct localization to strands that extend out from the region occupied by core junction proteins. We then discuss the implications for the protein network at the junction-cytoskeletal interface, suggesting different proteins localize and function in distinct ways but combine to produce robust connections.

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“…Therefore, we will hereafter use ‘cadherin’ to refer to type I classic cadherins, although some of these concepts may be generalizable to all classic cadherins. Extracellularly, cadherins can form trans bonds with cadherins on opposing cell membranes and cis bonds with cadherins on the same cell both of which are important for developing mature adhesions (Brasch et al, 2012; Troyanovsky, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…As an adhesion matures, cadherins organize into clusters, which is thought to strengthen adhesion (Brieher et al, 1996; Yap et al, 1998; Yap et al, 2015; Troyanovsky, 2022). Clustering is mediated extracellularly by the combined action of both trans and cis interactions (Wu et al, 2010; Wu et al, 2011; Wu et al, 2015), with additional intracellular contributions of p120 catenin (Ishiyama et al, 2010; Vu et al, 2021; Yap et al, 1998) and of the actin cytoskeleton (Truong Quang et al, 2013; Wu et al, 2015; Yap et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Dynamic remodelling of cadherin contacts in embryonic mesenchymal cells during differential cell migration

Rozema

Lasko

Fagotto

2023

Preprint

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A fundamental aspect of morphogenesis is the capacity of cells to actively exchange neighbours while maintaining the overall cohesion of the tissue. These cell rearrangements require the dynamic remodelling of cadherin cell adhesions. Many studies have examined this process in tissues where it is driven by the joint action of cell protrusions and actomyosin contraction along the shrinking junction. However, cell rearrangements can also occur through differential migration. This mode of cell rearrangement, characteristic of mesenchymal tissues, is much less well understood. Here, we explore the prototypical case of the gastrulating Xenopus prechordal mesoderm, and provide the first detailed analysis at how cadherin contacts are remodelled and eventually disrupted in this type of tissue. Using a reductionist approach, including analysis of single contacts using a dual pipette aspiration setup, we unveil two concurrent mechanisms. Most cadherins are removed via 'peeling', i.e. disruption of the trans bonds and lateral diffusion out of the contact. In parallel, a remnant of cadherins concentrates at the shrinking contact, which is ultimately resolved by breakage of the link with the actin cytoskeleton, showing that the weakest link shifts at different stages of contact remodelling. Additionally, we observe recruitment of myosin peripheral to the shrinking contact, which influences the efficiency of the final detachment. Finally, manipulation of cortical tension indicates that the process is sensitive to the magnitude and orientation of the forces applied on the contact, revealing another key relationship between cell-cell adhesion and the cortical cytoskeleton. This study unravels a new modality of cell contact dynamics, which is likely to be widely relevant for highly migratory mesenchymal tissues.

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Adherens junction: the ensemble of specialized cadherin clusters

Cited by 35 publications

References 147 publications

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules

Polychaetoid/ZO-1 strengthens cell junctions under tension while localizing differently than core adherens junction proteins

Dynamic remodelling of cadherin contacts in embryonic mesenchymal cells during differential cell migration

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