Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes

Nekrasova, Oxana; Amargo, Evangeline V.; Smith, William; Chen, Jing; Kreitzer, Geri; Green, Kathleen J.

doi:10.1083/jcb.20110605705302013c

Cited by 13 publications

(18 citation statements)

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“…This effect is seemingly attributable to the ability of DLK to regulate MT organization to the cell periphery since these defects were also reproduced in nocodazole-treated TESs, a model with impaired MT distribution to the cell periphery. The latter model further supports a role for MTs in the distribution of desmosomal cadherins (Nekrasova et al, 2011) and in the adequate barrier function of tight junctions (Sumigray et al, 2012). Finally, these results are also in agreement with previously reported desmosomal defects in the Lis1 e/e mouse epidermis, which displays reduced MT redistribution to the cell periphery (Sumigray et al, 2011).…”

Section: Discussionsupporting

confidence: 92%

A Role for DLK in Microtubule Reorganization to the Cell Periphery and in the Maintenance of Desmosomal and Tight Junction Integrity

Simard-Bisson

Bidoggia

Larouche

et al. 2017

Journal of Investigative Dermatology

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Dual leucine zipper-bearing kinase (DLK) is an inducer of keratinocyte differentiation, a complex process also involving microtubule reorganization to the cell periphery. However, signaling mechanisms involved in this process remain to be elucidated. Here, we demonstrate that DLK enhances and is required for microtubule reorganization to the cell periphery in human cell culture models and in Dlk knockout mouse embryos. In tissue-engineered skins with reduced DLK expression, cortical distribution of two microtubule regulators, LIS1 and HSP27, is impaired as well as desmosomal and tight junction integrity. Altered cortical distribution of desmosomal and tight junction proteins was also confirmed in Dlk knockout mouse embryos. Finally, desmosomal and tight junction defects were also observed after microtubule disruption in nocodazole-treated tissue-engineered skins, thus confirming a role for microtubules in the maintenance of these types of cell junctions. Globally, this study demonstrates that DLK is a key regulator of microtubule reorganization to the cell periphery during keratinocyte differentiation and that this process is required for the maintenance of desmosomal and tight junction integrity.

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Section: Discussionsupporting

confidence: 92%

A Role for DLK in Microtubule Reorganization to the Cell Periphery and in the Maintenance of Desmosomal and Tight Junction Integrity

Simard-Bisson

Bidoggia

Larouche

et al. 2017

Journal of Investigative Dermatology

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“…However, the translocation of desmoplakin to maturing desmosomes is kinesin-independent but involves actin and keratins [17,65]. Reciprocally, the microtubule network organization in the epidermis requires desmoplakin presence to stabilize desmosomes at the plasma membrane and favor keratin anchoring [66 ,67 ].…”

Section: Regulation Of Keratin-associated Adhesion Complexes By Cellumentioning

confidence: 99%

“…At the transport level for desmosomes, kinesins are required to transport desmosomal cadherins to the plasma membrane along microtubules [65]. However, the translocation of desmoplakin to maturing desmosomes is kinesin-independent but involves actin and keratins [17,65].…”

Section: Regulation Of Keratin-associated Adhesion Complexes By Cellumentioning

confidence: 99%

Remodeling of keratin-coupled cell adhesion complexes

Osmani

Labouesse

2015

Current Opinion in Cell Biology

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“…This indicates that different pathways exist for assembly of the desmosomal components. DP, probably by already attached keratin filaments, is translocated to the membrane by a mechanism involving initially Pkp3 and Epac1, followed by the concerted action of Pkp2, PKC and RhoA [4,22,54] In contrast, desmosomal cadherins are transported to the membrane by a microtubuledriven transport [39] and then laterally incorporated into desmosomes [47]. According to our data, at least Dsg3 is guided to the junctions by a mechanism that also requires E-cadherin and Src activity.…”

Section: Src and E-cadherin Regulate Dsg3 Assemblymentioning

confidence: 99%

E-cadherin and Src associate with extradesmosomal Dsg3 and modulate desmosome assembly and adhesion

Rötzer

Hartlieb

Vielmuth

et al. 2015

Cell. Mol. Life Sci.

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Desmosomes provide strong intercellular cohesion essential for the integrity of cells and tissues exposed to continuous mechanical stress. For desmosome assembly, constitutively synthesized desmosomal cadherins translocate to the cell-cell border, cluster and mature in the presence of Ca(2+) to stable cell contacts. As adherens junctions precede the formation of desmosomes, we investigated in this study the relationship between the classical cadherin E-cadherin and the desmosomal cadherin Desmoglein 3 (Dsg3), the latter of which is indispensable for cell-cell adhesion in keratinocytes. By using autoantibodies from patients with the blistering skin disease pemphigus vulgaris (PV), we showed in loss of function studies that E-cadherin compensates for effects of desmosomal disassembly. Overexpression of E-cadherin reduced the loss of cell cohesion induced by PV autoantibodies and attenuated activation of p38 MAPK. Silencing of E-cadherin abolished the localization of Dsg3 at the membrane and resulted in a shift of Dsg3 from the cytoskeletal to the non-cytoskeletal protein pool which conforms to the notion that E-cadherin regulates desmosome assembly. Mechanistically, we identified a complex consisting of extradesmosomal Dsg3, E-cadherin, β-catenin and Src and that the stability of this complex is regulated by Src. Moreover, Dsg3 and E-cadherin are phosphorylated on tyrosine residues in a Src-dependent manner and Src activity is required for recruiting Dsg3 to the cytoskeletal pool as well as for desmosome maturation towards a Ca(2+)-insensitive state. Our data provide new insights into the role of E-cadherin and the contribution of Src signaling for formation and maintenance of desmosomal junctions.

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Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes

Cited by 13 publications

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A Role for DLK in Microtubule Reorganization to the Cell Periphery and in the Maintenance of Desmosomal and Tight Junction Integrity

A Role for DLK in Microtubule Reorganization to the Cell Periphery and in the Maintenance of Desmosomal and Tight Junction Integrity

Remodeling of keratin-coupled cell adhesion complexes

E-cadherin and Src associate with extradesmosomal Dsg3 and modulate desmosome assembly and adhesion

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