ArticleApoptosis : an international journal on programmed cell death2019
Cornification of nail keratinocytes requires autophagy for bulk degradation of intracellular proteins while sparing components of the cytoskeleton.
Article in Apoptosis : an international journal on programmed cell death, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
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- Skin Appendage Proteins of Tetrapods: Building Blocks of Claws, Feathers, Hair and Other Cornified Epithelial Structures.Animals : an open access journal from MDPI · 2025Review
- Convergent Evolution Has Led to the Loss of Claw Proteins in Snakes and Worm Lizards.Genome biology and evolution · 2025Article
- Skin lamellar bodies: a unique set of lysosome-related organelles.Frontiers in cell and developmental biology · 2025Article
- Tissue-specific expression and functional role of keratin 1 in sheep horn development.Frontiers in veterinary science · 2025Article
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- Paraptosis: a unique cell death mode for targeting cancer.Frontiers in pharmacology · 2023Review
- Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer.Cells · 2022Article
- Disruption of actin dynamics induces autophagy of the eukaryotic chaperonin TRiC/CCT.Cell death discovery · 2022Article
- Witch Nails (Krt90whnl): A spontaneous mouse mutation affecting nail growth and development.PloS one · 2022Article
- mTORC1-chaperonin CCT signaling regulates mProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot.Biology · 2020Article
- Bafilomycin A1 Accelerates Chronic Refractory Wound Healing in db/db Mice.BioMed research international · 2020Article
- After-Death Functions of Cell Death.The Yale journal of biology and medicine · 2019Review
- Immunolocalization and phylogenetic profiling of the feather protein with the highest cysteine content.Protoplasma · 2019Article
- TRiC/CCT chaperonins are essential for organ growth by interacting with insulin/TOR signaling in Drosophila.Oncogene · 2019Article
- Autophagic Control of Skin Aging.Frontiers in cell and developmental biology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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