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5.
JAAD Case Rep ; 4(1): 58-60, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29387750
6.
J Cell Biol ; 209(3): 403-18, 2015 May 11.
Article in English | MEDLINE | ID: mdl-25963820

ABSTRACT

The linker of nucleoskeleton and cytoskeleton (LINC) complex allows cells to actively control nuclear position by coupling the nucleus to the cytoplasmic cytoskeleton. Nuclear position responds to the formation of intercellular adhesions through coordination with the cytoskeleton, but it is not known whether this response impacts adhesion function. In this paper, we demonstrate that the LINC complex component SUN2 contributes to the mechanical integrity of intercellular adhesions between mammalian epidermal keratinocytes. Mice deficient for Sun2 exhibited irregular hair follicle intercellular adhesions, defective follicle structure, and alopecia. Primary mouse keratinocytes lacking Sun2 displayed aberrant nuclear position in response to adhesion formation, altered desmosome distribution, and mechanically defective adhesions. This dysfunction appeared rooted in a failure of Sun2-null cells to reorganize their microtubule network to support coordinated intercellular adhesion. Together, these results suggest that cross talk between the nucleus, cytoskeleton, and intercellular adhesions is important for epidermal tissue integrity.


Subject(s)
Cell Nucleus/metabolism , Cytoskeleton/metabolism , Epidermis/metabolism , Keratinocytes/metabolism , Membrane Proteins/metabolism , Telomere-Binding Proteins/metabolism , Animals , Cell Adhesion/physiology , Cell Nucleus/genetics , Cytoskeleton/genetics , Epidermal Cells , Hair Follicle/cytology , Hair Follicle/metabolism , Keratinocytes/cytology , Membrane Proteins/genetics , Mice , Mice, Knockout , Telomere-Binding Proteins/genetics
7.
Mol Biol Cell ; 21(16): 2844-59, 2010 Aug 15.
Article in English | MEDLINE | ID: mdl-20554761

ABSTRACT

Plakophilin 2 (PKP2), an armadillo family member closely related to p120 catenin (p120ctn), is a constituent of the intercellular adhesive junction, the desmosome. We previously showed that PKP2 loss prevents the incorporation of desmosome precursors enriched in the plaque protein desmoplakin (DP) into newly forming desmosomes, in part by disrupting PKC-dependent regulation of DP assembly competence. On the basis of the observation that DP incorporation into junctions is cytochalasin D-sensitive, here we ask whether PKP2 may also contribute to actin-dependent regulation of desmosome assembly. We demonstrate that PKP2 knockdown impairs cortical actin remodeling after cadherin ligation, without affecting p120ctn expression or localization. Our data suggest that these defects result from the failure of activated RhoA to localize at intercellular interfaces after cell-cell contact and an elevation of cellular RhoA, stress fibers, and other indicators of contractile signaling in squamous cell lines and atrial cardiomyocytes. Consistent with these observations, RhoA activation accelerated DP redistribution to desmosomes during the first hour of junction assembly, whereas sustained RhoA activity compromised desmosome plaque maturation. Together with our previous findings, these data suggest that PKP2 may functionally link RhoA- and PKC-dependent pathways to drive actin reorganization and regulate DP-IF interactions required for normal desmosome assembly.


Subject(s)
Actomyosin/metabolism , Desmosomes/metabolism , Plakophilins/metabolism , rhoA GTP-Binding Protein/metabolism , Actins/metabolism , Animals , Cadherins/metabolism , Catenins/metabolism , Cell Communication , Cell Line , Cell Line, Tumor , Cytoskeleton/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Humans , Intercellular Junctions/metabolism , Microscopy, Fluorescence , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Myosin Light Chains/metabolism , Plakophilins/genetics , Protein Binding , Protein Kinase C/metabolism , RNA Interference , Signal Transduction , Delta Catenin
8.
Curr Opin Cell Biol ; 21(5): 708-16, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19674883

ABSTRACT

Armadillo family proteins known as plakophilins have been characterized as structural components of desmosomes that stabilize and strengthen adhesion by enhancing attachments with the intermediate filament cytoskeleton. However, plakophilins and their close relatives are emerging as versatile scaffolds for multiple signaling and metabolic processes that not only facilitate junction dynamics but also more globally regulate diverse cellular activities. While perturbation of plakophilin functions contribute to inherited diseases and cancer pathogenesis, the functional significance of the multiple PKP isoforms and the mechanisms by which their behaviors are regulated remain to be elucidated.


Subject(s)
Plakophilins/metabolism , Signal Transduction , Animals , Cell Adhesion , Disease Susceptibility/metabolism , Humans , Neoplasms/metabolism , Plakophilins/chemistry , Stress, Physiological
9.
J Cell Biol ; 181(4): 605-13, 2008 May 19.
Article in English | MEDLINE | ID: mdl-18474624

ABSTRACT

Plakophilins (PKPs) are armadillo family members related to the classical cadherin-associated protein p120(ctn). PKPs localize to the cytoplasmic plaque of intercellular junctions and participate in linking the intermediate filament (IF)-binding protein desmoplakin (DP) to desmosomal cadherins. In response to cell-cell contact, PKP2 associates with DP in plaque precursors that form in the cytoplasm and translocate to nascent desmosomes. Here, we provide evidence that PKP2 governs DP assembly dynamics by scaffolding a DP-PKP2-protein kinase C alpha (PKC alpha) complex, which is disrupted by PKP2 knockdown. The behavior of a phosphorylation-deficient DP mutant that associates more tightly with IF is mimicked by PKP2 and PKC alpha knockdown and PKC pharmacological inhibition, all of which impair junction assembly. PKP2 knockdown is accompanied by increased phosphorylation of PKC substrates, raising the possibility that global alterations in PKC signaling may contribute to pathogenesis of congenital defects caused by PKP2 deficiency.


Subject(s)
Desmosomes/enzymology , Plakophilins/metabolism , Protein Kinase C-alpha/metabolism , Cell Line , Desmoplakins/metabolism , Desmosomes/drug effects , Enzyme Activation/drug effects , Humans , Models, Biological , Protein Transport/drug effects , Serine/metabolism , Signal Transduction/drug effects , Tetradecanoylphorbol Acetate/pharmacology
10.
J Invest Dermatol ; 127(E1): E4-5, 2007 Jan 30.
Article in English | MEDLINE | ID: mdl-21270806
11.
J Invest Dermatol ; 127 Suppl 3: E4-5, 2007 Jan.
Article in English | MEDLINE | ID: mdl-26879540
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