Phosphorylation-dependent Pex11p and Fis1p interaction regulates peroxisome division.
Phosphorylation-dependent Pex11p and Fis1p interaction regulates peroxisome division.
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DOI：
10.1091/mbc.e11-09-0782
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发表时间：
2012-04
影响因子：
3.3
通讯作者：
Subramani S
中科院分区：
文献类型：
--
作者：
Joshi S;Agrawal G;Subramani S
Pex11p 在过氧化物酶体分裂中发挥保守作用。尽管 Pex11p 被磷酸化，但这种修饰的确切作用要么未知，要么令人困惑。毕赤酵母 Pex11p 在丝氨酸 173 处的磷酸化发生在过氧化物酶体上，并且是其与 Fis1p（过氧化物酶体分裂复合物的关键蛋白）相互作用所必需的。过氧化物酶体分裂受保守的过氧化物酶 Pex11p 调节。在酿酒酵母 (Sc) 中，磷蛋白 ScPex11p 的诱导与过氧化物酶体生物发生同时发生。我们发现毕赤酵母中的 ScPex11p 同源物 (PpPex11p) 在丝氨酸 173 处被磷酸化。PpPex11p 表达和磷酸化在油酸中被诱导，并与过氧化物酶体生物发生相协调。 PpPex11p 通过内质网 (ER) 转运至过氧化物酶体。 PpPex11p 不稳定，ER 限制 gin pex3Δ 和 pex19Δ 细胞，这些细胞的过氧化物酶体膜蛋白生物发生受损。在油酸培养基中，巴斯德毕赤酵母突变体 pex11A（组成型非磷酸化；S173A）和 pex11D（组成型磷酸化；S173D）分别表现出并列的细长过氧化物酶体 (JEP) 和超分裂形式，尽管蛋白质水平保持不变。与 ScPex11p 相比，毕赤酵母中的 ER 至过氧化物酶体易位是不依赖于磷酸化的，并且磷酸化发生在过氧化物酶体上。我们发现 PpPex11p 通过 PpFis1p 与过氧化物酶体裂变机制相互作用，并受到磷酸化的调节，因为 PpPex11p 和 PpPex11Dp 与 PpFis1p 的相互作用比 PpPex11Ap 更强。 PpPex11p 和 PpFis1p 都不是过氧化物酶体在甲醇介质中分裂所必需的。我们提出了一个模型，说明 PpPex11p 通过与裂变机制的磷酸化依赖性相互作用来调节过氧化物酶体分裂，为过氧化物酶体形态发生提供了新的见解。
Pex11p plays a conserved role in peroxisome division. Although Pex11p is phosphorylated, the exact role of this modification was either unknown or confusing. Phosphorylation of Pichia pastoris Pex11p at serine 173 occurs at the peroxisome and is necessary for its interaction with Fis1p, a key protein of the peroxisome division complex. Peroxisome division is regulated by the conserved peroxin Pex11p. In Saccharomyces cerevisiae (Sc), induction of the phosphoprotein ScPex11p coincides with peroxisome biogenesis. We show that the ScPex11p homologue in Pichia pastoris (PpPex11p) is phosphorylated at serine 173. PpPex11p expression and phosphorylation are induced in oleate and coordinated with peroxisome biogenesis. PpPex11p transits to peroxisomes via the endoplasmic reticulum (ER). PpPex11p is unstable and ER restricted gin pex3Δ and pex19Δ cells, which are impaired in peroxisomal membrane protein biogenesis. In oleate medium, the P. pastoris mutants pex11A (constitutively unphosphorylated; S173A) and pex11D (constitutively phosphorylated; S173D) exhibit juxtaposed elongated peroxisomes (JEPs) and hyperdivided forms, respectively, although protein levels remain unchanged. In contrast with ScPex11p, the ER-to-peroxisome translocation in P. pastoris is phosphorylation independent, and the phosphorylation occurs at the peroxisome. We show that PpPex11p interacts with the peroxisome fission machinery via PpFis1p and is regulated by phosphorylation because PpPex11p and PpPex11Dp interact more strongly with PpFis1p than PpPex11Ap. Neither PpPex11p nor PpFis1p is necessary for peroxisome division in methanol medium. We propose a model for the role of PpPex11p in the regulation of peroxisome division through a phosphorylation-dependent interaction with the fission machinery, providing novel insights into peroxisome morphogenesis.