• BMB Reports
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• v.49 no.6
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• pp.303-304
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• 2016

Myoblast fusion is important for skeletal muscle formation. Even though the knowledge of myoblast fusion mechanism has accumulated over the years, the initial signal of fusion is yet to be elucidated. Our study reveals the novel function of a phosphatidylserine (PS) receptor, stabilin-2 (Stab2), in the modulation of myoblast fusion, through the recognition of PS exposed on myoblasts. During differentiation of myoblasts, Stab2 expression is higher than other PS receptors and is controlled by calcineurin/NFAT signaling on myoblasts. The forced expression of Stab2 results in an increase in myoblast fusion; genetic ablation of Stab2 in mice causes a reduction in muscle size, as a result of impaired myoblast fusion. After muscle injury, muscle regeneration is impaired in Stab2-deficient mice, resulting in small myofibers with fewer nuclei, which is due to reduction of fusion rather than defection of myoblast differentiation. The fusion-promoting role of Stab2 is dependent on its PS-binding motif, and the blocking of PS-Stab2 binding impairs cell-cell fusion on myoblasts. Given our previous finding that Stab2 recognizes PS exposed on apoptotic cells for sensing as an "eat-me" signal, we propose that PS-Stab2 binding is required for sensing of a "fuse-me" signal as the initial signal of myoblast fusion.

• Genomics & Informatics
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• v.7 no.1
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• pp.20-25
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• 2009

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is characterized by inflammation of the synovial tissue and deterioration of the joint and bone. A recent study reported a potential gene-environment interaction between HLA-DR and smoking. The present study investigated whether a specific gene was related to the association between smoking and the severity of RA (rheumatoid factor levels > 20 IU/ml). We used the resources of the NARAC family collection of GAW 15 databases, and 1139 subjects with RF>20 IU/ml were included in the current analysis. The linkage panel contained 5858 SNP markers, and 5744 SNPs passed quality control criteria. Linear regression analyses, using PLINK software and generalized estimating equation regression models, were used to test for associations between the SNPs and the severity of RA according to smoking groups. Two major findings were established. First, the severity of RA in smokers was associated with rs703618 (p=$6{\times}10^{-5}$), which lies in the intronic region of the stabilin 2 (STAB2) gene on chromosome 12. Second, there were significant differences in the levels of RF between 'ever smokers' and 'never smokers' according to the rs703618 genotype (G/G, A/G, A/A). We investigated whether a specific gene acts as a mediator between smoking and the severity of RA and found that the STAB2 gene could affect this relationship. Our finding indicates that smoking may mediate RA severity by affecting the expression level of a specific gene.