Cysteinyl leukotriene receptor 1 is a potent regulator of the endosomal-lysosomal system in the ARPE-19 retinal pigment epithelial cell line.

IF 3.6 3区生物学 Q3 CELL BIOLOGY

Traffic Pub Date : 2023-04-01 DOI:10.1111/tra.12881

Andreas Koller, Susanne Maria Brunner, Julia Preishuber-Pflügl, Christian Runge, Anja-Maria Ladek, Herbert Anton Reitsamer, Andrea Trost

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引用次数: 2

Abstract

The endosomal-lysosomal system is central for cell homeostasis and comprises the functions and dynamics of particular organelles including endosomes, lysosomes and autophagosomes. In previous studies, we found that the cysteinyl leukotriene receptor 1 (CysLTR1) regulates autophagy in the retinal pigment epithelial cell line ARPE-19 under basal cellular conditions. However, the underlying mechanism by which CysLTR1 regulates autophagy is unknown. Thus, in the present study, the effects of CysLTR1 inhibition on the endosomal-lysosomal system are analyzed in detail to identify the role of CysLTR1 in cell homeostasis and autophagy regulation. CysLTR1 inhibition in ARPE-19 cells by Zafirlukast, a CysLTR1 antagonist, depleted the lysosomal pool. Furthermore, CysLTR1 antagonization reduced endocytic capacity and internalization of epidermal growth factor and decreased levels of the transferrin receptor, CD71. Serum starvation abolished the effect of Zafirlukast on the autophagic flux, which identifies the endocytic regulation of serum components by CysLTR1 as an important autophagy-modulating mechanism. The role of CysLTR1 in inflammation and cell stress has been exceedingly studied, but its involvement in the endosomal-lysosomal pathway is largely unknown. This current study provides new insights into basal activity of CysLTR1 on cellular endocytosis and the subsequent impact on downstream processes like autophagy.

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半胱氨酸白三烯受体1是ARPE-19视网膜色素上皮细胞系内溶酶体系统的有效调节剂。

核内体-溶酶体系统是细胞稳态的中心，包括核内体、溶酶体和自噬体等特定细胞器的功能和动力学。在之前的研究中，我们发现在基础细胞条件下，半胱氨酸白三烯受体1 (CysLTR1)调节视网膜色素上皮细胞系ARPE-19的自噬。然而，CysLTR1调控自噬的潜在机制尚不清楚。因此，在本研究中，我们将详细分析抑制CysLTR1对内体-溶酶体系统的影响，以确定CysLTR1在细胞稳态和自噬调节中的作用。CysLTR1拮抗剂Zafirlukast对ARPE-19细胞的CysLTR1抑制作用耗尽了溶酶体库。此外，CysLTR1拮抗剂降低了内吞能力和表皮生长因子的内化，降低了转铁蛋白受体CD71的水平。血清饥饿消除了Zafirlukast对自噬通量的影响，这表明CysLTR1对血清成分的内吞调节是一种重要的自噬调节机制。CysLTR1在炎症和细胞应激中的作用已被广泛研究，但其在内体-溶酶体途径中的作用在很大程度上是未知的。本研究对CysLTR1在细胞内吞作用中的基础活性及其对自噬等下游过程的影响提供了新的见解。

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来源期刊

Traffic 生物-细胞生物学

CiteScore

8.10

自引率

2.20%

发文量

审稿时长

2 months

期刊介绍： Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.