{"title":"Functional Differences Between SIRPα Splice Isoforms","authors":"Mihoko Kajita, Yojiro Matsui, Kotaro Sugimoto, Shuto Takeuchi, Shota Matsumoto, Takahiro Okumura, Hiroyuki Kajiura, Kazuki Motomura, Atsushi Takeda, Tomomi Koshiyama, Kyoko Shirakabe","doi":"10.1111/gtc.70041","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 5","pages":""},"PeriodicalIF":1.3000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70041","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes to Cells","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/gtc.70041","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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.
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.