Secreted D-aspartate oxidase functions in C. elegans reproduction and development
Secreted D-aspartate oxidase functions in C. elegans reproduction and development
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分泌型 D-天冬氨酸氧化酶在秀丽隐杆线虫繁殖和发育中的功能
DOI：
10.1111/febs.14691
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Homma Hiroshi
中科院分区：
文献类型：
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作者：
Saitoh Yasuaki;Katane Masumi;Miyamoto Tetsuya;Sekine Masae;Sakamoto Taro;Imai Hirotaka;Homma Hiroshi
d-天冬氨酸氧化酶（DDO）是一种立体专一性地作用于D-氨基酸（如d-天冬氨酸和d-谷氨酸）的降解酶，在调节哺乳动物的神经传递、发育过程、激素分泌和生殖功能中起重要作用。相比之下，d-谷氨酸在哺乳动物中的生理作用仍不清楚。在秀丽隐杆线虫中，负责d-谷氨酸体内代谢的酶是DDO-3，这是三种DDO同工型之一，也是正常自我繁殖，孵化和寿命所必需的。通常，真核DDO以过氧化物酶体靶向信号类型1（PTS 1）依赖性方式定位于亚细胞过氧化物酶体。然而，DDO-3不含PTS 1，而是具有推定的N末端信号肽（SP）。在这项研究中，我们发现DDO-3是一种分泌型DDO，这是在真核生物中描述的第一种此类酶。在雌雄同体动物中，DDO-3以SP依赖性方式从近端性腺鞘细胞分泌并转移到卵母细胞表面。在雄性中，DDO-3在与雌雄同体交配期间以SP依赖性方式从精囊分泌到精液中。在两种性别中，DDO-3从细胞分泌，在细胞中产生进入体液并被清道夫体腔细胞摄取。全长DDO-3转基因挽救了由缺失DDO-3引起的所有表型，而缺乏推定SP的DDO-3转基因则没有。总之，这些结果表明DDO-3的分泌对其生理功能至关重要。
d‐Aspartate oxidase (DDO) is a degradative enzyme that acts stereospecifically on free acidic D‐amino acids such asd‐aspartate andd‐glutamate.d‐Aspartate plays an important role in regulating neurotransmission, developmental processes, hormone secretion, and reproductive functions in mammals. In contrast, the physiological role ofd‐glutamate in mammals remains unclear. InCaenorhabditis elegans, the enzyme responsible forin vivometabolism ofd‐glutamate is DDO‐3, one of the three DDO isoforms, which is also required for normal self‐fertility, hatching, and lifespan. In general, eukaryotic DDOs localize to subcellular peroxisomes in a peroxisomal targeting signal type 1 (PTS1)‐dependent manner. However, DDO‐3 does not contain a PTS1, but instead has a putative N‐terminal signal peptide (SP). In this study, we found that DDO‐3 is a secreted DDO, the first such enzyme to be described in eukaryotes. In hermaphrodites, DDO‐3 was secreted from the proximal gonadal sheath cells in a SP‐dependent manner and transferred to the oocyte surface. In males, DDO‐3 was secreted from the seminal vesicle into the seminal fluid in a SP‐dependent manner during mating with hermaphrodites. In both sexes, DDO‐3 was secreted from the cells where it was produced into the body fluid and taken up by scavenger coelomocytes. Full‐length DDO‐3 transgene rescued all phenotypes elicited by the deletion ofddo‐3, whereas a DDO‐3 transgene lacking the putative SP did not. Together, these results indicate that secretion of DDO‐3 is essential for its physiological functions.