PAK4 Regulates Actin and Microtubule Dynamics during Meiotic Maturation in Mouse Oocyte

He, Yating; Yang, Leilei; Luo, Shi‐Ming; Shen, Wei; Yin, Shen; Sun, Qing‐Yuan

doi:10.7150/ijbs.34718

Cited by 7 publications

(3 citation statements)

References 40 publications

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“…The PAK family consists of six members, PAK1 to PAK6 [24]. PAK1, PAK2, and PAK4 have been reported to exist in mammalian oocytes [15,25]. In the current study, we identified that activated PAK1 exhibited a dynamic distribution and expression during meiosis in porcine oocytes.…”

Section: Discussionmentioning

confidence: 51%

PAK1-Dependent Regulation of Microtubule Organization and Spindle Migration Is Essential for the Metaphase I–Metaphase II Transition in Porcine Oocytes

Peng,

He,

Wang

et al. 2024

Biomolecules

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P21-activated kinase 1 (PAK1) is a critical downstream target that mediates the effect of small Rho GTPase on the regulation of cytoskeletal kinetics, cell proliferation, and cell migration. PAK1 has been identified as a crucial regulator of spindle assembly during the first meiotic division; however, its roles during the metaphase I (MI) to metaphase II (MII) transition in oocytes remain unclear. In the present study, the potential function of PAK1 in regulating microtubule organization and spindle positioning during the MI–MII transition was addressed in porcine oocytes. The results showed that activated PAK1 was co-localized with α-tubulin, and its expression was increased from the MI to MII stage (p < 0.001). However, inhibiting PAK1 activity with an inhibitor targeting PAK1 activation-3 (IPA-3) at the MI stage decreased the first polar body (PB1) extrusion rate (p < 0.05), with most oocytes arrested at the anaphase-telophase (ATI) stage. IPA-3-treated oocytes displayed a decrease in actin distribution in the plasma membrane (p < 0.001) and an increase in the rate of defects in MII spindle reassembly with abnormal spindle positioning (p < 0.001). Nevertheless, these adverse effects of IPA-3 on oocytes were reversed when the disulfide bond between PAK1 and IPA-3 was reduced by dithiothreitol (DTT). Co-immunoprecipitation revealed that PAK1 could recruit activated Aurora A and transform acidic coiled-coil 3 (TACC3) to regulate spindle assembly and interact with LIM kinase 1 (LIMK1) to facilitate actin filament-mediated spindle migration. Together, PAK1 is essential for microtubule organization and spindle migration during the MI–MII transition in porcine oocytes, which is associated with the activity of p-Aurora A, p-TACC3 and p-LIMK1.

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Section: Discussionmentioning

confidence: 51%

PAK1-Dependent Regulation of Microtubule Organization and Spindle Migration Is Essential for the Metaphase I–Metaphase II Transition in Porcine Oocytes

Peng,

He,

Wang

et al. 2024

Biomolecules

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“…The migration and positioning of the meiotic spindle at the cortex of the oocyte are crucial for asymmetric division, with actin microfilaments assuming a vital role in spindle migration [ 15 , 16 ]. As the meiotic spindle forms near the center of the cell, actin microfilaments accumulate around the periphery of the spindle and form actin flows, which facilitate spindle migration from the center to the cortex [ 17 ]. Actin filaments, initially evenly distributed in the oocyte cortex, become polarized during spindle migration.…”

Section: Introductionmentioning

confidence: 99%

Sirtuin 5-driven meiotic spindle assembly and actin-based migration in mouse oocyte meiosis

Ma,

Zhang,

Zhang

et al. 2024

Heliyon

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“…High quality oocytes are essential for successful fertilization, early embryo survival and healthy fetal development [3]. However, many defects can damage oocyte maturation, including oxidative stress, apoptosis, endoplasmic reticulum (ER) stress and mitochondrial dysfunction [4][5][6]. Thus, the quality of oocytes is the major determinant of female reproductive potential.…”

Section: Introductionmentioning

confidence: 99%

Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway

Duan

Wang

et al. 2023

J Animal Sci Biotechnol

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Background Zearalenone (ZEA) widely exists in moldy grains, which seriously destroys the fertility of females. Isorhamnetin, a natural flavonoid, has extensive of pharmacological activities. However, the beneficial effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced porcine oocyte damage have not been investigated. Methods Oocytes were treated with different concentrations of ZEA (3, 5, 8 and 10 μmol/L) and isorhamnetin (5, 10, 20 and 30 μmol/L) for 44 h at 39 ℃. ZEA (5 μmol/L) and isorhamnetin (10 μmol/L) were selected for subsequent studies. Polar body exclusion rate, apoptosis rate and apoptosis related proteins, ROS levels and SOD2 protein, mitochondrial membrane potential and distribution, endoplasmic reticulum distribution and proteins expression, and PI3K, Akt and p-Akt proteins expression of oocytes were detected. In addition, the effect of PI3K antagonist (LY294002) on oocyte nuclear maturation and apoptosis were used to determine the involvement of PI3K/Akt signaling pathway. Results Our findings showed that ZEA exposure damaged oocytes and isorhamnetin therapy restored the developmental capability of porcine oocytes. Isorhamnetin promoted polar body extrusion rate to rescue ZEA-induced meiotic arrest in porcine oocytes. Isorhamnetin alleviated ZEA-induced oxidative stress by stimulating SOD2 protein expression and inhibiting ROS production. Moreover, isorhamnetin enhanced normal mitochondrial distribution and mitochondrial membrane potential to prevent mitochondrial dysfunction induced by ZEA. Changing the expression of endoplasmic reticulum stress-related marker proteins (CHOP, GRP78) and the distribution rate of normal endoplasmic reticulum showed that isorhamnetin relieved ZEA-caused endoplasmic reticulum stress. Mechanistically, isorhamnetin decreased Bax/Bcl-2 protein expression and inhibited ZEA-induced apoptosis through PI3K/Akt signaling pathway. Conclusions Collectively, these results suggest that isorhamnetin protects oocytes from ZEA-caused damage through PI3K/Akt signaling pathway, which enhances meiotic maturation and mitochondrial function, and inhibits early apoptosis, oxidative stress and endoplasmic reticulum stress in porcine oocytes. Our study provides a new strategy for solving the reproductive toxicity induced by ZEA and treating woman infertility. Graphical Abstract A possible mechanism by which isorhamnetin protected porcine oocytes from ZEA-induced damage. Isorhamnetin inhibited meiosis arrest and apoptosis of porcine oocytes induced by ZEA through the PI3K/Akt signaling pathway. Moreover, isorhamnetin repaired ZEA-induced oocyte damage by alleviating oxidative stress, mitochondrial dysfunction and ER stress.

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PAK4 Regulates Actin and Microtubule Dynamics during Meiotic Maturation in Mouse Oocyte

Cited by 7 publications

References 40 publications

PAK1-Dependent Regulation of Microtubule Organization and Spindle Migration Is Essential for the Metaphase I–Metaphase II Transition in Porcine Oocytes

PAK1-Dependent Regulation of Microtubule Organization and Spindle Migration Is Essential for the Metaphase I–Metaphase II Transition in Porcine Oocytes

Sirtuin 5-driven meiotic spindle assembly and actin-based migration in mouse oocyte meiosis

Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway

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