Dual role of valosin-containing protein (VCP/p97) in mouse sperm during capacitation.

IF 3.7 3区生物学 Q1 DEVELOPMENTAL BIOLOGY

Reproduction Pub Date : 2024-07-13 Print Date: 2024-08-01 DOI:10.1530/REP-24-0069

Martina Jabloñski, Florenza A La Spina, Liza J Schiavi-Ehrenhaus, Clara I Marín-Briggiler, Matias D Gomez-Elias, Dario Krapf, Pablo E Visconti, Diego Krapf, Guillermina M Luque, Mariano G Buffone

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引用次数: 0

Abstract

Valosin-containing protein (VCP; aka p97), a member of the AAA (ATPases Associated with various cellular Activities) family, has been associated with a wide range of cellular functions. While previous evidence has shown its presence in mammalian sperm, our study unveils its function in mouse sperm. Notably, we found that mouse VCP does not undergo tyrosine phosphorylation during capacitation and exhibits distinct localization patterns. In the sperm head, it resides within the equatorial segment and, following acrosomal exocytosis, it is released and cleaved. In the flagellum, VCP is observed in the principal and midpiece. Furthermore, our research highlights a unique role for VCP in the cAMP/PKA pathway during capacitation. Pharmacological inhibition of sperm VCP led to reduced intracellular cAMP levels that resulted in decreased phosphorylation in PKA substrates and tyrosine residues and diminished fertilization competence. Our results show that in mouse sperm, VCP plays a pivotal role in regulating cAMP production, probably by the modulation of soluble adenylyl cyclase activity.

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含缬氨酸蛋白（VCP/p97）在小鼠精子获能过程中的双重作用

含缬氨酸蛋白（VCP，又名 p97）是 AAA 家族（与各种细胞活动有关的 ATP 酶）的成员，与多种细胞功能有关。以前的证据表明它存在于哺乳动物的精子中，而我们的研究揭示了它在小鼠精子中的功能。值得注意的是，我们发现小鼠的 VCP 在获能过程中不会发生酪氨酸磷酸化，并表现出独特的定位模式。在精子头部，它位于赤道段内，在外分泌后被释放并裂解。在鞭毛中，VCP 位于主片和中片。此外，我们的研究还强调了 VCP 在获能过程中 cAMP/PKA 通路中的独特作用。药物抑制精子 VCP 会导致细胞内 cAMP 水平降低，从而导致 PKA 底物和酪氨酸残基的磷酸化减少，受精能力降低。我们的研究结果表明，在小鼠精子中，VCP可能通过调节可溶性腺苷酸环化酶（sAC）的活性，在调节cAMP的产生方面起着关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproduction 生物-发育生物学

CiteScore

7.40

自引率

2.60%

发文量

199

审稿时长

4-8 weeks

期刊介绍： Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction. Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease. Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.