Suppression of autophagy perturbs turnover of sequestosome-1/p62 in Merkel cells but not in keratinocytes

Sukseree, Supawadee; Bergmann, Sophie; Pajdzik, Kinga; Tschachler, Erwin; Eckhart, Leopold

doi:10.1016/j.jdermsci.2018.01.008

Cited by 11 publications

(9 citation statements)

References 10 publications

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“…Together with results of other reports (Rossiter et al, 2013;Sukseree et al, 2018), this study shows that epithelial cell types of the skin have different requirements for autophagy. Differences in the rate of cell turnover are likely to explain why the suppression of epithelial autophagy in Atg7-KO mice caused an accumulation of p62 in www.jidonline.org 2061 LETTERS TO THE EDITOR eccrine glands, but not in epidermal keratinocytes.…”

supporting

confidence: 87%

“…Suppression of autophagy in mice that carry a floxed Atg7 gene and the K14-Cre transgene (Atg7 f/f K14-Cre) to delete Atg7 in keratinocytes, leads to thickening of the epidermis without skin barrier impairment (Rossiter et al, 2013). In contrast to epidermal keratinocytes, Atg7-deficient thymic epithelial cells and Merkel cells display accumulations of sequestosome-1/p62 (Sukseree et al, 2012(Sukseree et al, , 2018, a well-established autophagy substrate and regulator of important cellular processes, such as protein turnover, Nrf2 signaling, and NF-kB signaling (Katsuragi et al, 2015).…”

mentioning

confidence: 99%

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Suppression of Epithelial Autophagy Compromises the Homeostasis of Sweat Glands during Aging

Sukseree

Bergmann

Pajdzik

et al. 2018

Journal of Investigative Dermatology

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supporting

confidence: 87%

mentioning

confidence: 99%

Suppression of Epithelial Autophagy Compromises the Homeostasis of Sweat Glands during Aging

Sukseree

Bergmann

Pajdzik

et al. 2018

Journal of Investigative Dermatology

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“…They differentiate from epithelial cells that express keratin K5/K14 and switch to a K8/K18-dependent cytoskeleton. Merkel cells reside in the basal layer where they are either organized in touch domes or in circular arrangement in the upper part of the hair fiber (Sukseree et al, 2018b). Upon physical stimulation, they release serotonergic vesicles at synapses with nerve fibers that transmit the signal further (Figure 1).…”

Section: Autophagy In Epithelial Cells Of the Skinmentioning

confidence: 99%

“…Upon physical stimulation, they release serotonergic vesicles at synapses with nerve fibers that transmit the signal further (Figure 1). It was hypothesized that autophagy is active in Merkel cells to degrade a fraction of serotonergic vesicles and thereby to control the strength of signaling at serotonergic synapses (Sukseree et al, 2018b). The sensation of soft touch is important for spatial awareness and communication.…”

Section: Autophagy In Epithelial Cells Of the Skinmentioning

confidence: 99%

Autophagic Control of Skin Aging

Eckhart

Tschachler

Грубер

2019

Front. Cell Dev. Biol.

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The skin forms the barrier to the environment. Maintenance of this barrier during aging requires orchestrated responses to variable types of stress, the continuous renewal of the epithelial compartment, and the homeostasis of long-lived cell types. Recent experimental evidence suggests that autophagy is critically involved in skin homeostasis and skin aging is associated with and partially caused by defects of autophagy. In the outer skin epithelium, autophagy is constitutively active during cornification of keratinocytes and increases the resistance to environmental stress. Experimental suppression of autophagy in the absence of stress is tolerated by the rapidly renewing epidermal epithelium, whereas long-lived skin cells such as melanocytes, Merkel cells and secretory cells of sweat glands depend on autophagy for cellular homeostasis and normal execution of their functions during aging. Yet other important roles of autophagy have been identified in the dermis where senescence of mesenchymal cells and alterations of the extracellular matrix (ECM) are hallmarks of aging. Here, we review the evidence for cell type-specific roles of autophagy in the skin and their differential contributions to aging.

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“…Suppression of epithelial autophagy even led to premature degradation of the nucleus in sebocytes [ 15 , 16 ]. In addition, the stratum corneum of Atg7 f / f K14-Cre mice was thickened [ 14 ], and the protein turnover in thymic epithelial cells [ 17 ], sweat glands [ 18 ], Merkel cells [ 19 ], and sebaceous glands [ 20 ] was altered. The autophagy adapter and substrate proteins microtubule-associated proteins 1A/1B light chain 3A (LC3) and sequestosome 1 (Sqstm1)/p62 were elevated in isolated epidermal keratinocytes upon deletion of autophagy genes [ 15 , 21 ], but a comprehensive catalog of keratinocyte proteins targeted by autophagy has remained elusive.…”

Section: Introductionmentioning

confidence: 99%

Cornification of nail keratinocytes requires autophagy for bulk degradation of intracellular proteins while sparing components of the cytoskeleton

et al. 2018

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Epidermal keratinocytes undergo cornification to form the cellular building blocks of hard skin appendages such as nails and the protective layer on the surface of the skin. Cornification requires the cross-linking of structural proteins and the removal of other cellular components to form mechanically rigid and inert corneocytes. Autophagy has been proposed to contribute to this intracellular remodelling process, but its molecular targets in keratinocytes, if any, have remained elusive. Here, we deleted the essential autophagy factor Atg7 in K14-positive epithelia of mice and determined by proteomics the impact of this deletion on the abundance of individual proteins in cornified nails. The genetic suppression of autophagy in keratinocytes resulted in a significant increase in the number of proteins that survived cornification and in alterations of their abundance in the nail proteome. A broad range of enzymes and other non-structural proteins were elevated whereas the amounts of cytoskeletal proteins of the keratin and keratin-associated protein families, cytolinker proteins and desmosomal proteins were either unaltered or decreased in nails of mice lacking epithelial autophagy. Among the various types of non-cytoskeletal proteins, the subunits of the proteasome and of the TRiC/CCT chaperonin were most strongly elevated in mutant nails, indicating a particularly important role of autophagy in removing these large protein complexes during normal cornification. Taken together, the results of this study suggest that autophagy is active during nail keratinocyte cornification and its substrate specificity depends on the accessibility of proteins outside of the cytoskeleton and their presence in large complexes. Electronic supplementary material The online version of this article (10.1007/s10495-018-1505-4) contains supplementary material, which is available to authorized users.

show abstract

Suppression of autophagy perturbs turnover of sequestosome-1/p62 in Merkel cells but not in keratinocytes

Cited by 11 publications

References 10 publications

Suppression of Epithelial Autophagy Compromises the Homeostasis of Sweat Glands during Aging

Suppression of Epithelial Autophagy Compromises the Homeostasis of Sweat Glands during Aging

Autophagic Control of Skin Aging

Cornification of nail keratinocytes requires autophagy for bulk degradation of intracellular proteins while sparing components of the cytoskeleton

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