Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine Stimulation

In starfish oocytes, the hormone 1-methyladenine (1-MA) induces germinal vesicle breakdown (GVBD) through a signaling cascade involving PI3K, SGK, Cdc25, and Cdk1/cyclin via G-proteinβγ subunit. Following GVBD, fertilization triggers an intracellular calcium increase, leading to the formation of the...

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Main Authors: Sakurako Aida, Takako Matsumoto, Yuna Yamazaki, Nunzia Limatola, Luigia Santella, Kazuyoshi Chiba
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/6/405
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author Sakurako Aida
Takako Matsumoto
Yuna Yamazaki
Nunzia Limatola
Luigia Santella
Kazuyoshi Chiba
author_facet Sakurako Aida
Takako Matsumoto
Yuna Yamazaki
Nunzia Limatola
Luigia Santella
Kazuyoshi Chiba
author_sort Sakurako Aida
collection DOAJ
description In starfish oocytes, the hormone 1-methyladenine (1-MA) induces germinal vesicle breakdown (GVBD) through a signaling cascade involving PI3K, SGK, Cdc25, and Cdk1/cyclin via G-proteinβγ subunit. Following GVBD, fertilization triggers an intracellular calcium increase, leading to the formation of the fertilization envelope (FE) via cortical granule exocytosis. While transient calcium elevations are known to occur after 1-MA stimulation even without fertilization, the inability of these calcium elevations to induce cortical granule exocytosis and FE formation remained unexplained. In this study, we found that co-treatment with 1-MA and calcium ionophore A23187 prevents FE formation, revealing a transient period termed the “no FE phase” persisting for several minutes. After no FE phase, the oocytes regain full competence to form the FE. Furthermore, we identified that the GEF/Rac1 signaling cascade is activated during the no FE phase. Notably, constitutively active Rac1 expressed in oocytes reproduces this inhibition even in the absence of 1-MA stimulation. These findings suggest that the GEF/Rac1 cascade, triggered by 1-MA, initiates the no FE phase and plays a critical role in coordinating the progression of subsequent fertilization events.
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spelling doaj-art-702ed71e66d64db3aab1c9955e1783792025-08-20T02:42:42ZengMDPI AGCells2073-44092025-03-0114640510.3390/cells14060405Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine StimulationSakurako Aida0Takako Matsumoto1Yuna Yamazaki2Nunzia Limatola3Luigia Santella4Kazuyoshi Chiba5Department of Biological Sciences, Ochanomizu University, Tokyo 112-8610, JapanDepartment of Biological Sciences, Ochanomizu University, Tokyo 112-8610, JapanDepartment of Biological Sciences, Ochanomizu University, Tokyo 112-8610, JapanDepartment of Research Infrastructures for Marine Biological Resources, Stazione Zoologica Anton Dohrn, 80121 Napoli, ItalyDepartment of Research Infrastructures for Marine Biological Resources, Stazione Zoologica Anton Dohrn, 80121 Napoli, ItalyDepartment of Biological Sciences, Ochanomizu University, Tokyo 112-8610, JapanIn starfish oocytes, the hormone 1-methyladenine (1-MA) induces germinal vesicle breakdown (GVBD) through a signaling cascade involving PI3K, SGK, Cdc25, and Cdk1/cyclin via G-proteinβγ subunit. Following GVBD, fertilization triggers an intracellular calcium increase, leading to the formation of the fertilization envelope (FE) via cortical granule exocytosis. While transient calcium elevations are known to occur after 1-MA stimulation even without fertilization, the inability of these calcium elevations to induce cortical granule exocytosis and FE formation remained unexplained. In this study, we found that co-treatment with 1-MA and calcium ionophore A23187 prevents FE formation, revealing a transient period termed the “no FE phase” persisting for several minutes. After no FE phase, the oocytes regain full competence to form the FE. Furthermore, we identified that the GEF/Rac1 signaling cascade is activated during the no FE phase. Notably, constitutively active Rac1 expressed in oocytes reproduces this inhibition even in the absence of 1-MA stimulation. These findings suggest that the GEF/Rac1 cascade, triggered by 1-MA, initiates the no FE phase and plays a critical role in coordinating the progression of subsequent fertilization events.https://www.mdpi.com/2073-4409/14/6/405starfishoocyte maturationRac1actincalciumfertilization
spellingShingle Sakurako Aida
Takako Matsumoto
Yuna Yamazaki
Nunzia Limatola
Luigia Santella
Kazuyoshi Chiba
Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine Stimulation
Cells
starfish
oocyte maturation
Rac1
actin
calcium
fertilization
title Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine Stimulation
title_full Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine Stimulation
title_fullStr Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine Stimulation
title_full_unstemmed Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine Stimulation
title_short Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine Stimulation
title_sort rac1 temporarily suppresses fertilization envelope formation immediately after 1 methyladenine stimulation
topic starfish
oocyte maturation
Rac1
actin
calcium
fertilization
url https://www.mdpi.com/2073-4409/14/6/405
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