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2022 - The role of LRRC8 in the hypotonic stress response of human keratinocytes

 icon sp96  SyncroPatch 384 poster, Europhysiology 2022  logo pdf   (1.07 MB)

Background:

The human skin is constantly exposed to various stress factors such as temperature changes, mechanical stress, different humidity levels, air pollution or radiation. These factors can have a tremendous impact on the skin and can contribute to barrier disruption and inflammation, dry and fragile skin as well as premature ageing (Rosso et al., 2016). Recent advances in different research areas point to an impor­tant role of LRRC8 volume regulated anion channels (VRACs) in a plethora of different physiological processes (Chen et al., 2019). The function of LRRC8 has been characterized in human keratinocytes and in the native human epidermis (Trothe et al., 2018) and the LRRC8 ion channel has been proposed to be a novel molecular target to modulate keratinocyte differ­entiation. LRRC8A (also named SWELL1) has been identified as the first essential component of VRACs in various cell types (Qui et al., 2014; Voss et al., 2014). LRRC8A is composed of four transmembrane domains and a C-terminal domain containing up to 17 leucine-rich repeats. Together with four additional LRRC8 family members (LRRC8B-E) it assembles into hetero-hexameric complexes (Qiu et al., 2014; Voss et al., 2014). The LRRC8 subunit composi­tion differs between cell types and influences VRAC prop­erties such as inactivation kinetics, voltage-dependence and selectivity of the transported osmolyte. The gen­eration of LRRC8A-/- knockout HaCaT keratinocytes has provided evidence for the essential function of LRRC8A in hypotonic stress response of human keratinocytes (Trothe et al., 2018).

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