CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.
Junxiong ChenYingjun DingChao JiangRongmei QuJonathan D WrenConstantin GeorgescuXuejun WangDarlene N ReuterBeibei LiuCory B GilesChristoph H MayrHerbert B SchillerJingxing DaiChristopher S StippBharathiraja SubramaniyanJie WangHoujuan ZuoChao HuangKar-Ming FungHeather C RiceArnoud SonnenbergDavid WuMatthew S WaltersYou-Yang ZhaoTomoharu KanieFranklin A HaysJames F PapinDao-Wen WangXin A ZhangPublished in: Circulation research (2024)
Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells determines vascular information. Thus, the IFITM3/V-ATPase-tetraspanin-VCP/p97 complexes on endolysosome, as a protein quality control and inflammation-inhibitory machinery, could be beneficial for therapeutic intervention against vascular inflammation.