Ran Tao, Alan D Robertson, William Fuller, Caglar Gök
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引用次数: 0
摘要
细胞Ca2+稳态对正常细胞生理至关重要，并受到多种机制的调节。多个组织中细胞内Ca2+稳态的两个主要参与者属于SLC8 （Na+/Ca2+交换器（nxs））；NCX1-3)和SLC24 (K+依赖性Na+/Ca2+交换剂（NCKXs）；NCKX1-5)的家庭。已经确定NCXs和NCKX4是棕榈酰化的，棕榈酰化促进NCX1失活。然而，对于NCKXs的棕榈酰化作用，目前所知甚少。我们发现(1)NCKX3和NCKX5存在棕榈酰化，而NCKX1不存在；(2)NCXK3和NCKX5的467和325位点的Cys to Ala突变显著降低了棕榈酰化；(3)棕榈酰化的降低增强了NCKX3的活性。我们的研究结果为NCKX1、NCKX3和NCKX5棕榈酰化提供了新的见解，并确立了棕榈酰化是NCKX3活性的内源性调节因子，为研究评估棕榈酰化在NCKX3健康和疾病功能中的作用铺平了道路。
Palmitoylation and regulation of potassium dependent sodium/calcium exchangers (NCKX).
Cellular Ca2+ homeostasis is critical for normal cell physiology and is regulated by several mechanisms. Two major players in intracellular Ca2+ homeostasis in multiple tissues belong to SLC8 (Na+/Ca2+ exchangers (NCXs); NCX1-3) and SLC24 (K+ dependent Na+/Ca2+ exchangers (NCKXs); NCKX1-5) families. It has been established that NCXs and NCKX4 are palmitoylated, and that palmitoylation promotes NCX1 inactivation. However, there is still little known about NCKXs' palmitoylation. We found that (1) NCKX3 and NCKX5 but not NCKX1 are palmitoylated, (2) Cys to Ala mutation at position 467 for NCXK3 and 325 for NCKX5 notably diminished palmitoylation and (3) reduced palmitoylation enhanced NCKX3 activity. Our findings bring novel insights on NCKX1, NCKX3 and NCKX5 palmitoylation, and establish palmitoylation as endogenous regulator of NCKX3 activity, paving the way for investigations evaluating the role of palmitoylation in NCKX3 function in health and disease.
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