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Genodermatoses affecting the nail
Published in Eckart Haneke, Histopathology of the NailOnychopathology, 2017
In the ectodermal dysplasia-skin fragility syndrome, a plakophilin-1 mutation leads to hair and teeth abnormalities. The nails become thickened. Histologically a widening of the intercellular spaces between the keratinocytes from the suprabasal to the granular layer is observed (Figure 6.7).109
Desmosomes undergo dynamic architectural changes during assembly and maturation
Published in Tissue Barriers, 2022
Reena R. Beggs, Tejeshwar C. Rao, William F. Dean, Andrew P. Kowalczyk, Alexa L. Mattheyses
The second architectural feature we quantified from the dSTORM images was desmosome length. There was a cell line-dependent difference in how the desmosome length changed with maturation: the length increased as E-cadherin was sorted out only in MDCK cells. Changes in the length are not unexpected, and an increase in desmosome length has also been observed in plakophilin 1 overexpression-induced hyperadhesion for example.31 However, it is not known how desmosome length is regulated, and cell-type specific differences are possible. When interpreting our data, it is important to note that the doubling time of MDCK cells (~30 h) is approximately half that of NHEK or HUC cells (~60-115 h).32–34 It is conceivable that the increase in the plaque length is a universal feature, which is not correlated with E-cadherin exclusion or adhesion but our timeline was not long enough to capture this in the NHEK and HUC cell lines.
Skin proteomics – analysis of the extracellular matrix in health and disease
Published in Expert Review of Proteomics, 2020
Jörn Dengjel, Leena Bruckner-Tuderman, Alexander Nyström
As protein phosphorylation is a major determinant of protein activation and regulator of protein–protein interactions its analysis has received a lot of attention. MS-based proteomic approaches are the method of choice to study alterations in the phosphorylation status of proteins giving rise to the research field of phosphoproteomics [129]. As for expression proteomic experiments, initial studies addressing protein phosphorylation in skin cells were coupled to 2D-PAGE [130]. Especially the effect of irradiation on skin cells was analyzed by phosphoproteomic approaches, highlighting that skin fibroblasts respond differentially to low and high doses of ionizing radiation [131,132]. Later, phosphoproteomic approaches were coupled with elegant mechanistic studies. E.g. in mouse skin and mouse keratinocytes Polo-like Kinase 1 (Plk1) was identified to regulate keratinocyte planar cell polarity by phosphorylating the protein Celsr1, regulating its endosomal recruitment during mitosis [133]. Specific phosphorylation events were also shown to be important for skin cell differentiation: the kinase CSNK1a1 was shown to be important for keratinocyte progenitor maintenance by phosphorylating protein arginine methyltransferase 1 (PRMT1) [134]; receptor-interacting serine-threonine kinase 4 (Ripk4) was identified to phosphorylate the desmosome component plakophilin-1 (Pkp1) in mouse keratinocyte differentiation [135]. Absence of either of the two proteins led to enhanced epidermal carcinogenesis.