Classical Cadherins Regulate Desmosome Formation

Michels, Christian; Buchta, Thomas; Bloch, Wilhelm; Krieg, Thomas; Niessen, Carien M.

doi:10.1038/jid.2009.17

Cited by 52 publications

(68 citation statements)

References 13 publications

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“…A longstanding theory suggests that intercellular contacts established between classic cadherins at adherens junctions, structures which resemble desmosomes architecturally, must occur before desmosome initiation. Lending support to this hypothesis, adherens junctions appear prior to desmosomes during embryogenesis and genetic disruption of classic cadherin function leads to aberrant desmosome formation in several model systems (Fleming et al, 1994;Lewis et al, 1997;Amagai et al, 1995;Michels et al, 2009). Plakoglobin uniquely localizes to both desmosomes and adherens junctions.…”

Section: Assembly: Requirements For Initiating Desmosome Assemblymentioning

confidence: 82%

Structural and Functional Diversity of Desmosomes

Harmon

Green

2013

Cell Communication & Adhesion

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Section: Assembly: Requirements For Initiating Desmosome Assemblymentioning

confidence: 82%

Structural and Functional Diversity of Desmosomes

Harmon

Green

2013

Cell Communication & Adhesion

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“…Previous results have shown that loss of plakoglobin leads to the depletion of desmosomal proteins from the cell border and to defects in desmosome formation (Acehan et al, 2008;Gosavi et al, 2011;Knudsen and Wheelock, 1992;Lewis et al, 1997). Although the presence of a classical cadherin seems to be required for plakoglobin recruitment to the cell border (Michels et al, 2009;Tinkle et al, 2008), the mechanisms by which plakoglobin is transported have not been identified. The results presented here suggest that phosphorylation of plakoglobin by PKCm at residue S236 leads to the generation of a binding site for 14-3-3c, and that 14-3-3c is required for the transport of plakoglobin to the cell border in order to initiate desmosome formation, presumably in a complex with a classical cadherin (Michels et al, 2009;Tinkle et al, 2008).…”

Section: Discussionmentioning

confidence: 98%

“…Ruiz and colleagues have reported that the epidermis of embryos at 11.5 days post coitum are normal upon loss of plakoglobin (Ruiz et al, 1996), whereas others have reported that defects in epidermal organization and desmosome function are observed in mice lacking plakoglobin at 17.5 days post coitum (Bierkamp et al, 1996). Plakoglobin has been reported to form a complex with both P-cadherin and E-cadherin, and the total levels of the classical cadherins dictate desmosome formation and organization (Lewis et al, 1997;Michels et al, 2009;Tinkle et al, 2008). These results suggest that plakoglobin and other ARM proteins might serve as a link between adherens junction formation and desmosome formation.…”

Section: Introductionmentioning

confidence: 99%

14-3-3γ meditated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo

Sehgal

Mukhopadhyay

Rajan

et al. 2014

Journal of Cell Science

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The regulation of cell-cell adhesion is important for the processes of tissue formation and morphogenesis. Here we report that loss of 14-3-3γ leads to a decrease in cell-cell adhesion and a defect in the transport of plakoglobin (PG) and other desmosomal proteins to the cell border in HCT116 cells and in the mouse testis. 14-3-3γ binds to PG in a PKCμ dependent fashion resulting in microtubule dependent transport of PG to the border. Transport of PG to the border is dependent on the KIF5B/KLC1 complex. Knockdown of KIF5B in HCT116 cells or in the mouse testis, results in a phenotype similar to that observed with 14-3-3γ knockdown. Our results suggest that loss of 14-3-3γ leads to decreased desmosome formation and a decrease in cell-cell adhesion in vitro and in vivo in the mouse testis leading to defects in testis organization and spermatogenesis.

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“…Although our data show that E-cadherin is necessary to reorganize traction forces, E-cadherin alone may not be sufficient. Further study is required to determine whether additional adhesive processes downstream of adherens junctions, such as the formation of desmosomes by nonclassical cadherins (47), are necessary to achieve sufficient cohesion.…”

Section: Discussionmentioning

confidence: 99%

Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces

Mertz¹,

Che²,

Banerjee³

et al. 2012

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

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219

201

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Cell-cell and cell-matrix adhesions play essential roles in the function of tissues. There is growing evidence for the importance of cross talk between these two adhesion types, yet little is known about the impact of these interactions on the mechanical coupling of cells to the extracellular matrix (ECM). Here, we combine experiment and theory to reveal how intercellular adhesions modulate forces transmitted to the ECM. In the absence of cadherin-based adhesions, primary mouse keratinocytes within a colony appear to act independently, with significant traction forces extending throughout the colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a cohesive colony localize traction forces to the colony periphery. Through genetic or antibody-mediated loss of cadherin expression or function, we show that cadherin-based adhesions are essential for this mechanical cooperativity. A minimal physical model in which cell-cell adhesions modulate the physical cohesion between contractile cells is sufficient to recreate the spatial rearrangement of traction forces observed experimentally with varying strength of cadherin-based adhesions. This work defines the importance of cadherin-based cell-cell adhesions in coordinating mechanical activity of epithelial cells and has implications for the mechanical regulation of epithelial tissues during development, homeostasis, and disease. mechanotransduction | traction force microscopy M echanical interactions of individual cells have a crucial role in the spatial organization of tissues (1, 2) and in embryonic development (3-5). The mechanical cooperation of cells is evident in dynamic processes such as flow-induced alignment of vascular endothelial cells (6) and muscle contraction (7). However, mechanical interactions of cells within a tissue also affect the tissue's static mechanical properties including elastic modulus (8), surface tension (9), and fracture toughness (10). Little is known about how these tissue-scale mechanical phenomena emerge from interactions at the molecular and cellular levels (11).Tissue-scale mechanical phenomena are particularly important in developmental morphogenesis (12), homeostasis (13), and wound healing (14) in epithelial tissues. Cells exert mechanical force on each other at sites of intercellular adhesion, typically through cadherins (15, 16), as well as on the underlying extracellular matrix (ECM) through integrins (17-19). Cadherin-based adhesions can alter physical aspects of cells such as the surface tension of cellular aggregates (20) and the spreading (21) and migration (22) of single cells adherent to cadherin-patterned substrates. Integrity of intercellular adhesions may also contribute to metastatic potential (23). We and others have shown that epithelial cell clusters with strong cell-cell adhesions exhibit coordinated mechanical behavior over length scales much larger than a single cell (24-27). Several studies have implicated cross talk between cell-ECM and cell-cell adhesions (28, 29) that can be modulated by ac...

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Classical Cadherins Regulate Desmosome Formation

Cited by 52 publications

References 13 publications

Structural and Functional Diversity of Desmosomes

Structural and Functional Diversity of Desmosomes

14-3-3γ meditated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo

Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces

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