Nucleophagy: A New Look at Past Observations

Han, Pei; Lavker, Robert M.

doi:10.1016/j.jid.2016.04.019

Cited by 7 publications

(4 citation statements)

References 21 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the final steps in stratified squamous epithelial differentiation is the removal of nuclei (Lavker and Matoltsy, 1970). This process, now termed nucleophagy, is a form of autophagy and plays a key role in the terminal differentiation of epidermal keratinocytes (Akinduro et al, 2016, Peng and Lavker, 2016). Consistent with the positive role of autophagy in epidermal terminal differentiation, GFP-LC3 levels in differentiated layers of the epidermis are dramatically higher than the basal layer (Figures 1a and 2a) (Rossiter et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs-103/107 Regulate Autophagy in the Epidermis

Wang

Kobeissi

Dong

et al. 2018

Journal of Investigative Dermatology

Self Cite

View full text Add to dashboard Cite

We have shown that microRNAs-103 and -107 (miRs-103/107) positively regulate end-stage autophagy by ensuring dynamin activity in cultured keratinocytes. Most work in end-stage autophagy has been conducted using in vitro model systems. In vivo regulation of end-stage autophagy in epidermis remains unknown. Here, we used antagomirs to subcutaneously knock down miR-107 in the skin; conversely, we delivered miR-107 mimic subcutaneously via in vivo transfection to increase this miR. We found that antagomir-107 treatment in epidermis: (i) depleted endogenous miR-107; (ii) increased GFP-LC3 puncta in epidermal basal layers of GFP-LC3 transgenic mice, indicative of an accumulation of autophagosomes; (iii) inhibited LC3 turnover and increased p62, suggesting an inhibition of autophagy flux; and (iv) increased phosphorylated dynamin (p-dynamin, an inactive form), a key enzyme in end-stage autophagy. Conversely, miR-107 mimic treatment in mouse epidermis: decreased GFP-LC3 puncta in basal layer, as well as p62 protein levels; and diminished p-dynamin, indicative of activation of this enzyme. In human epidermal keratinocytes, antagos-103/107 cause the formation of large vacuoles and an increase in p-dynamin, which can be rescued by inhibition of protein kinase C pathway. Collectively, these results suggest that the miR-103/107 family has a critical role in regulating end-stage autophagy in mouse epidermis via PLD1/2-protein kinase C-dynamin pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNAs-103/107 Regulate Autophagy in the Epidermis

Wang

Kobeissi

Dong

et al. 2018

Journal of Investigative Dermatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, this process has only been documenting early stages of nuclear removal and there may be other mechanisms essential for complete degradation of the nucleus [ 8 ].…”

Section: Epidermal Keratinocyte Nuclear Removalmentioning

confidence: 99%

“…1 ). The mammalian nucleophagic mechanisms have until recently been relatively unclear and whether these processes are involved, perhaps with several other mechanisms, for complete nuclear loss remains to be characterised [ 8 ]. These three cell types are the only cells in mammalian tissues known to entirely remove their nucleus under normal physiological conditions, yet, little is known about nuclear removal in these cell types, the regulation of these pathways and whether they share common features.…”

mentioning

confidence: 99%

Uncovering mechanisms of nuclear degradation in keratinocytes: A paradigm for nuclear degradation in other tissues

Rogerson

Bergamaschi

O'Shaughnessy

2018

Nucleus

View full text Add to dashboard Cite

Eukaryotic nuclei are essential organelles, storing the majority of the cellular DNA, comprising the site of most DNA and RNA synthesis, controlling gene expression and therefore regulating cellular function. The majority of mammalian cells retain their nucleus throughout their lifetime, however, in three mammalian tissues the nucleus is entirely removed and its removal is essential for cell function. Lens fibre cells, erythroblasts and epidermal keratinocytes all lose their nucleus in the terminal differentiation pathways of these cell types. However, relatively little is known about the pathways that lead to complete nuclear removal and about how these pathways are regulated. In this review, we aim to discuss the current understanding of nuclear removal mechanisms in these three cell types and expand upon how recent studies into nuclear degradation in keratinocytes, an easily accessible experimental model, could contribute to a wider understanding of these molecular mechanisms in both health and pathology.

show abstract

“… 82 Recently, the molecular machinery involved in the removal of nuclei (nucleophagy) during the end-stages of keratinization have been detailed and this form of autophagy was demonstrated to be induced when keratinocytes differentiate. 83 , 84 Taken together these observations raise questions of how autophagy is regulated in the corneal epithelium and the role of autophagy and nucleophagy in corneal epithelial differentiation. We have preliminary evidence implicating a regulatory role for miR-184, which is the most highly expressed corneal epithelial miRNA.…”

Section: Ingestion/digestion: Gaps In Knowledge From An Anterior Oculmentioning

confidence: 99%

Autophagy and Macropinocytosis: Keeping an Eye on the Corneal/Limbal Epithelia

Han

Park

Lavker

2017

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

Autophagy and macropinocytosis are processes that are vital for cellular homeostasis, and help cells respond to stress and take up large amounts of material, respectively. The limbal and corneal epithelia have the machinery necessary to carry out both processes; however, autophagy and macropinocytosis are relatively understudied in these two epithelia. In this Perspectives, we describe the basic principles behind macropinocytosis and autophagy, discuss how these two processes are regulated in the limbal and corneal epithelia, consider how these two processes impact on the physiology of limbal and corneal epithelia, and elaborate on areas of future research in autophagy and macropinocytosis as related to the limbal/corneal epithelia.

show abstract

Nucleophagy: A New Look at Past Observations

Cited by 7 publications

References 21 publications

MicroRNAs-103/107 Regulate Autophagy in the Epidermis

MicroRNAs-103/107 Regulate Autophagy in the Epidermis

Uncovering mechanisms of nuclear degradation in keratinocytes: A paradigm for nuclear degradation in other tissues

Autophagy and Macropinocytosis: Keeping an Eye on the Corneal/Limbal Epithelia

Contact Info

Product

Resources

About