TASL mediates keratinocyte differentiation by regulating intracellular calcium levels and lysosomal function

Ji Yeong Park, Hyeng Soo Kim, Hyejin Hyung, Soyeon Jang, Jiwon Ko, Jin Hong Lee, Si Yong Kim, Song Park, Junkoo Yi, Sijun Park, Su Geun Lim, Seonggon Kim, Sanggyu Lee, Myoung Ok Kim, Soyoung Jang, Zae Young Ryoo

Research output: Contribution to journalArticlepeer-review

Abstract

Maintaining epidermal homeostasis relies on a tightly organized process of proliferation and differentiation of keratinocytes. While past studies have primarily focused on calcium regulation in keratinocyte differentiation, recent research has shed light on the crucial role of lysosome dysfunction in this process. TLR adaptor interacting with SLC15A4 on the lysosome (TASL) plays a role in regulating pH within the endo-lysosome. However, the specific role of TASL in keratinocyte differentiation and its potential impact on proliferation remains elusive. In our study, we discovered that TASL deficiency hinders the proliferation and migration of keratinocytes by inducing G1/S cell cycle arrest. Also, TASL deficiency disrupts proper differentiation process in TASL knockout human keratinocyte cell line (HaCaT) by affecting lysosomal function. Additionally, our research into calcium-induced differentiation showed that TASL deficiency affects calcium modulation, which is essential for keratinocyte regulation. These findings unveil a novel role of TASL in the proliferation and differentiation of keratinocytes, providing new insights into the intricate regulatory mechanisms of keratinocyte biology.

Original languageEnglish
Article number10978
JournalScientific Reports
Volume14
Issue number1
DOIs
StatePublished - Dec 2024

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