Activity of long-chain acyl-CoA synthetase is required for maintaining meiotic arrest in Xenopus laevis.
In most vertebrates, fully grown oocytes are arrested in meiotic prophase I and only resume the cell cycle upon external stimuli, such as hormones. The proper arrest and resumption of the meiotic cycle is critical for reproduction. A Galpha(S) signaling pathway essential for the arrest is conserved in organisms from Xenopus to mouse and human. A previous gene association study implicated that mutations of human ACSL6 may be related to premature ovarian failure. However, functional roles of ACSL6 in human infertility have yet to be reported. In the present study, we found that triacsin C, a potent and specific inhibitor for ACSL, triggers maturation in Xenopus and mouse oocytes in the absence of hormone, suggesting ACSL activity is required for the oocyte arrest. In Xenopus, acsl1b may fulfill a major role in the process, because inhibition of acsl1b by knocking down its RNA results in abnormal acceleration of oocyte maturation. Such abnormally matured eggs cannot support early embryonic development. Moreover, direct inhibition of protein palmitoylation, which lies downstream of ACSLs, also causes oocyte maturation. Furthermore, palmitoylation of Galpha(s), which is essential for its function, is inhibited when the ACSL activity is blocked by triacsin C in Xenopus. Thus, disruption of ACSL activity causes inhibition of the Galpha(s) signaling pathway in the oocytes, which may result in premature ovarian failure in human.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Hua-wei
HW
Wang
Jun-shun
JS
Fang
Xia
X
Kuang
Li-yun
LY
Miao
Chao
C
Wang
Guo-liang
GL
Xia
Mary Lou
ML
King
Jian
J
Zhang
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian; D004789:Enzyme Activation; D005260:Female; D059471:In Vitro Oocyte Maturation Techniques; D008540:Meiosis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009865:Oocytes / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D023121:RNA, Messenger, Stored / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D000214:Acyl Coenzyme A; C113822:PGAT protein, Xenopus; D023121:RNA, Messenger, Stored; D014157:Transcription Factors; D029867:Xenopus Proteins; D003066:Coenzyme A Ligases