Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells.
Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells.
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小鼠卵母细胞和颗粒细胞中 IMPDH2 Cytohophidium 的协调形成
DOI：
10.3389/fcell.2021.690536
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发表时间：
2021
影响因子：
5.5
通讯作者：
Su YQ
中科院分区：
文献类型：
--
作者：
Ni S;Zhang T;Zhou C;Long M;Hou X;You L;Li H;Shi L;Su YQ
肌苷单磷酸脱氢酶（IMPDH）是催化鸟嘌呤核苷酸从头生物合成的限速酶，在某些情况下会在几种类型的细胞中聚集成一种非膜丝状宏观结构，称为“胞质丝状体”或“杆环结构”。然而，IMPDH组装成胞质丝状体的生物学意义和潜在机制仍然不清楚。据报道，在小鼠卵巢中，IMPDH通过为颗粒细胞的利钠肽C/利钠肽受体2（NPPC/NPR2）系统提供GTP底物以产生维持卵母细胞减数分裂停滞的cGMP，对维持卵母细胞 - 卵泡发育同步至关重要。因此，卵巢中的卵母细胞和相关体细胞为探索细胞内IMPDH胞质丝状体形成的功能意义提供了一个令人兴奋的模型系统。我们在此报告，IMPDH2胞质丝状体在体内自然生长的卵母细胞中以及在体外用IMPDH抑制剂霉酚酸（MPA）处理的卵丘包裹的卵母细胞中形成。抑制卵母细胞和着床前胚胎中的IMPDH活性分别损害卵母细胞的减数分裂和发育能力以及胚胎超过4细胞阶段的发育。在促黄体生成素（LH）激增后，IMPDH胞质丝状体也在排卵前卵泡的颗粒细胞体内形成，这与卵母细胞减数分裂的恢复和IMPDH2蛋白表达的降低同时发生。在培养的卵丘卵母细胞复合体（COCs）中，MPA处理导致卵丘细胞中同时形成IMPDH胞质丝状体以及卵母细胞减数分裂的恢复，这是由MTOR途径介导的，并且可以通过补充鸟苷来阻止。因此，我们的结果表明，胞质丝状体确实在发育的特定阶段在卵母细胞和颗粒细胞中形成，这可能分别有助于卵母细胞获得减数分裂和发育能力以及LH激增诱导减数分裂重新启动。
Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme catalyzing de novo biosynthesis of guanine nucleotides, aggregates under certain circumstances into a type of non-membranous filamentous macrostructure termed “cytoophidium” or “rod and ring” in several types of cells. However, the biological significance and underlying mechanism of IMPDH assembling into cytoophidium remain elusive. In mouse ovaries, IMPDH is reported to be crucial for the maintenance of oocyte–follicle developmental synchrony by providing GTP substrate for granulosa cell natriuretic peptide C/natriuretic peptide receptor 2 (NPPC/NPR2) system to produce cGMP for sustaining oocyte meiotic arrest. Oocytes and the associated somatic cells in the ovary hence render an exciting model system for exploring the functional significance of formation of IMPDH cytoophidium within the cell. We report here that IMPDH2 cytoophidium forms in vivo in the growing oocytes naturally and in vitro in the cumulus-enclosed oocytes treated with IMPDH inhibitor mycophenolic acid (MPA). Inhibition of IMPDH activity in oocytes and preimplantation embryos compromises oocyte meiotic and developmental competences and the development of embryos beyond the 4-cell stage, respectively. IMPDH cytoopidium also forms in vivo in the granulosa cells of the preovulatory follicles after the surge of luteinizing hormone (LH), which coincides with the resumption of oocyte meiosis and the reduction of IMPDH2 protein expression. In cultured COCs, MPA-treatment causes the simultaneous formation of IMPDH cytoopidium in cumulus cells and the resumption of meiosis in oocytes, which is mediated by the MTOR pathway and is prevented by guanosine supplementation. Therefore, our results indicate that cytoophidia do form in the oocytes and granulosa cells at particular stages of development, which may contribute to the oocyte acquisition of meiotic and developmental competences and the induction of meiosis re-initiation by the LH surge, respectively.
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MTOR 卵母细胞阶段特异性影响决定小鼠颗粒细胞命运和卵母细胞质量
DOI：
10.1073/pnas.1800352115
发表时间：
2018-06-05
影响因子：
11.1
作者：
Guo J;Zhang T;Guo Y;Sun T;Li H;Zhang X;Yin H;Cao G;Yin Y;Wang H;Shi L;Guo X;Sha J;Eppig JJ;Su YQ
通讯作者：
Su YQ
影响因子：
5.3
作者：
Hsieh, Minnie;Lee, Daekee;Conti, Marco
通讯作者：
Conti, Marco
影响因子：
5.3
作者：
Gu, JJ;Tolin, AK;Mitchell, BS
通讯作者：
Mitchell, BS
影响因子：
3.7
作者：
Carcamo WC;Satoh M;Kasahara H;Terada N;Hamazaki T;Chan JY;Yao B;Tamayo S;Covini G;von Mühlen CA;Chan EK
通讯作者：
Chan EK
影响因子：
3.6
作者：
Egbert JR;Uliasz TF;Shuhaibar LC;Geerts A;Wunder F;Kleiman RJ;Humphrey JM;Lampe PD;Artemyev NO;Rybalkin SD;Beavo JA;Movsesian MA;Jaffe LA
通讯作者：
Jaffe LA