Cornification of nail keratinocytes requires autophagy for bulk degradation of intracellular proteins while sparing components of the cytoskeleton
| العنوان: | Cornification of nail keratinocytes requires autophagy for bulk degradation of intracellular proteins while sparing components of the cytoskeleton |
|---|---|
| المؤلفون: | Brett S. Phinney, Florian Gruber, Karin Jaeger, Robert H. Rice, Marie Sophie Narzt, Shaomin Zhong, Supawadee Sukseree, Erwin Tschachler, Maria Buchberger, Veronika Mlitz, Leopold Eckhart |
| المصدر: | Apoptosis : an international journal on programmed cell death, vol 24, iss 1-2 Apoptosis |
| بيانات النشر: | eScholarship, University of California, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Keratinocytes, Proteomics, Cancer Research, Cytoplasm, Hoof and Claw, Organogenesis, Clinical Biochemistry, Medical Physiology, Intracellular Space, Cornification, Pharmaceutical Science, Nail, Inbred C57BL, Chaperonin, Mice, 0302 clinical medicine, Keratin, Cytoskeleton, Skin, chemistry.chemical_classification, Mice, Knockout, integumentary system, Cell Differentiation, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Proteome, Keratins, Keratinocyte, Biochemistry & Molecular Biology, Knockout, Article, 03 medical and health sciences, medicine, Autophagy, Animals, Pharmacology, Corneocyte, Biochemistry (medical), Inbred CBA, Cell Biology, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Proteasome, Proteolysis, Mice, Inbred CBA, Generic health relevance, Biochemistry and Cell Biology, Epidermis |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::383bc90b9266b7793f378bcaba69d39fTest https://escholarship.org/uc/item/0fk9m9qqTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....383bc90b9266b7793f378bcaba69d39f |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |