Mahanty, S and Dakappa, SS and Shariff, R and Patel, S and Swamy, MM and Majumdar, A and Setty, SRG (2019) Keratinocyte differentiation promotes ER stress-dependent lysosome biogenesis. In: Cell Death and Disease, 10 (10).
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Abstract
Keratinocytes maintain epidermal integrity through cellular differentiation. This process enhances intraorganelle digestion in keratinocytes to sustain nutritional and calcium-ionic stresses observed in upper skin layers. However, the molecular mechanisms governing keratinocyte differentiation and concomitant increase in lysosomal function is poorly understood. Here, by using primary neonatal human epidermal keratinocytes, we identified the molecular link between signaling pathways and cellular differentiation/lysosome biogenesis. Incubation of keratinocytes with CaCl2 induces differentiation with increased cell size and early differentiation markers. Further, differentiated keratinocytes display enhanced lysosome biogenesis generated through ATF6-dependent ER stress signaling, but independent of mTOR-MiT/TFE pathway. In contrast, chemical inhibition of mTORC1 accelerates calcium-induced keratinocyte differentiation, suggesting that activation of autophagy promotes the differentiation process. Moreover, differentiation of keratinocytes results in lysosome dispersion and Golgi fragmentation, and the peripheral lysosomes showed colocalization with Golgi-tethering proteins, suggesting that these organelles possibly derived from Golgi. In line, inhibition of Golgi function, but not the depletion of Golgi-tethers or altered lysosomal acidity, abolishes keratinocyte differentiation and lysosome biogenesis. Thus, ER stress regulates lysosome biogenesis and keratinocyte differentiation to maintain epidermal homeostasis.
| Item Type: | Journal Article |
|---|---|
| Publication: | Cell Death and Disease |
| Publisher: | Nature Publishing Group |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 19 Oct 2022 09:01 |
| Last Modified: | 19 Oct 2022 09:01 |
| URI: | https://eprints.iisc.ac.in/id/eprint/77348 |
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