Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Eur J Cell Biol. 2011 Oct;90(10):844-53. doi: 10.1016/j.ejcb.2011.06.002.
Several glycolytic enzymes and their isoforms have been found to be important in cell signaling unrelated to glycolysis. The involvement of parafusin (PFUS), a member of the phosphoglucomutase (PGM) superfamily with no phosphoglucomutase activity, in Ca(2+)-dependent exocytosis has been controversial. This protein was first described in Paramecium tetraurelia, but is widely found. Earlier work showed that parafusin is a secretory vesicle scaffold component with unusual post-translational modifications (cyclic phosphorylation and phosphoglucosylation) coupled to stages in the exocytic process. Using RNAi, we demonstrate that parafusin synthesis can be reversibly blocked, with minor or no effect on other PGM isoforms. PFUS knockdown produces an inhibition of dense core secretory vesicle (DCSV) synthesis leading to an exo(-) phenotype. Although cell growth is unaffected, vesicle content is not packaged properly and no new DCSVs are formed. We conclude that PFUS and its orthologs are necessary for proper scaffold maturation. Because of this association, parafusin is an important signaling component for regulatory control of the secretory pathway.
几种糖酵解酶及其同工酶已被发现与糖酵解无关的细胞信号传导中很重要。与磷酸葡萄糖变位酶（PGM）超家族成员无磷酸葡萄糖变位酶活性的 parafusin（PFUS）参与 Ca（2+）依赖性胞吐作用一直存在争议。这种蛋白质最初在四膜虫 Paramecium tetraurelia 中被描述，但广泛存在。早期的研究表明，parafusin 是一种分泌囊泡支架成分，具有与胞吐过程阶段相关的异常翻译后修饰（环状磷酸化和磷酸葡萄糖基化）。使用 RNAi，我们证明 parafusin 合成可以被可逆阻断，对其他 PGM 同工酶几乎没有影响或没有影响。PFUS 敲低导致致密核心分泌囊泡（DCSV）合成抑制，导致 exo(-)表型。尽管细胞生长不受影响，但囊泡内容物没有正确包装，并且没有形成新的 DCSVs。我们得出结论，PFUS 及其同源物是适当支架成熟所必需的。由于这种关联，parafusin 是调节分泌途径的信号成分的重要组成部分。
