Functional Differences Between SIRPα Splice Isoforms

IF 1.3 4区 生物学 Q4 CELL BIOLOGY
Genes to Cells Pub Date : 2025-08-05 DOI:10.1111/gtc.70041
Mihoko Kajita, Yojiro Matsui, Kotaro Sugimoto, Shuto Takeuchi, Shota Matsumoto, Takahiro Okumura, Hiroyuki Kajiura, Kazuki Motomura, Atsushi Takeda, Tomomi Koshiyama, Kyoko Shirakabe
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引用次数: 0

Abstract

Signal regulatory protein (SIRP) α, an inhibitory receptor belonging to the immunoglobulin (Ig) superfamily is abundantly expressed in phagocytes such as macrophages. CD47, the ligand for SIRPα, is expressed in most healthy cells, and called “don't eat me” signal because it binds to SIRPα on the surface of macrophages and inhibits phagocytosis. SIRPα has multiple splice isoforms, but most functional analyses have been carried out using long SIRPα, the SIRPα isoform with three extracellular Ig domains. In this study, we analyzed the expression and function of short SIRPα, an SIRPα isoform with only one extracellular Ig domain. In resting mouse macrophage Raw 264.7 cells, the short and long SIRPα mRNA expression levels were similar, and the proportion of short SIRPα mRNA decreased substantially after endotoxin stimulation. Short SIRPα bound to CD47 as same as long SIRPα, however, did not suppress the phagocytosis of recombinant CD47-coated beads, unlike long SIRPα. These results suggest that short SIRPα may be a “don't eat me” signal regulator with different expression and function from long SIRPα.

Abstract Image

SIRPα剪接异构体的功能差异
信号调节蛋白(SIRP) α是免疫球蛋白(Ig)超家族的一种抑制受体,在巨噬细胞等吞噬细胞中大量表达。CD47是SIRPα的配体,在大多数健康细胞中表达,被称为“不要吃我”信号,因为它与巨噬细胞表面的SIRPα结合并抑制吞噬作用。SIRPα具有多个剪接异构体,但大多数功能分析都使用具有三个细胞外Ig结构域的SIRPα长异构体进行。在这项研究中,我们分析了短SIRPα的表达和功能,SIRPα是一种只有一个细胞外Ig结构域的SIRPα亚型。在静息小鼠巨噬细胞Raw 264.7细胞中,短SIRPα mRNA和长SIRPα mRNA的表达水平相似,内毒素刺激后短SIRPα mRNA的比例明显下降。然而,与长SIRPα不同,短SIRPα与CD47结合并不能抑制重组CD47包被珠的吞噬作用。这些结果表明,短SIRPα可能是一种“不要吃我”的信号调节剂,其表达和功能与长SIRPα不同。
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来源期刊
Genes to Cells
Genes to Cells 生物-细胞生物学
CiteScore
3.40
自引率
0.00%
发文量
71
审稿时长
3 months
期刊介绍: Genes to Cells provides an international forum for the publication of papers describing important aspects of molecular and cellular biology. The journal aims to present papers that provide conceptual advance in the relevant field. Particular emphasis will be placed on work aimed at understanding the basic mechanisms underlying biological events.
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