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VCP/p97 在小鼠精子获能过程中的双重作用。

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

机构信息

Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

Instituto de Biología Molecular y Celular de Rosario, CONICET-UNR, Rosario, Argentina.

出版信息

Reproduction. 2024 Jul 13;168(2). doi: 10.1530/REP-24-0069. Print 2024 Aug 1.

DOI:10.1530/REP-24-0069
PMID:38912971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11425197/
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.

摘要

包含缬氨酸的蛋白（VCP；又名 p97）是 AAA（与各种细胞活动相关的 ATP 酶）家族的成员，与广泛的细胞功能相关。尽管先前的证据表明它存在于哺乳动物精子中，但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 VCP 在获能过程中不会发生酪氨酸磷酸化，并且表现出不同的定位模式。在精子头部，它位于赤道段内，在顶体反应后，它被释放并被切割。在鞭毛中，VCP 存在于主段和中段。此外，我们的研究强调了 VCP 在获能过程中在 cAMP/PKA 途径中的独特作用。通过药理学抑制精子 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。我们的结果表明，在小鼠精子中，VCP 发挥关键作用，调节 cAMP 的产生，可能通过调节可溶性腺苷酸环化酶的活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/030268bfd5d2/nihms-2014548-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/d6db6309333d/nihms-2014548-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/a00c46d74009/nihms-2014548-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/7f18a4f6c18a/nihms-2014548-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/35e872c0da91/nihms-2014548-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/1867682945bb/nihms-2014548-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/030268bfd5d2/nihms-2014548-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/d6db6309333d/nihms-2014548-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/a00c46d74009/nihms-2014548-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/7f18a4f6c18a/nihms-2014548-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/35e872c0da91/nihms-2014548-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/1867682945bb/nihms-2014548-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dfa/11425197/030268bfd5d2/nihms-2014548-f0006.jpg

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Membrane Remodeling and Matrix Dispersal Intermediates During Mammalian Acrosomal Exocytosis.哺乳动物顶体胞吐过程中的膜重塑和基质分散中间体
Front Cell Dev Biol. 2021 Dec 10;9:765673. doi: 10.3389/fcell.2021.765673. eCollection 2021.
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Cdc42 localized in the CatSper signaling complex regulates cAMP-dependent pathways in mouse sperm.
定位于精子阳离子通道（CatSper）信号复合物中的Cdc42调节小鼠精子中依赖环磷酸腺苷（cAMP）的信号通路。
FASEB J. 2021 Aug;35(8):e21723. doi: 10.1096/fj.202002773RR.
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NMS-873 functions as a dual inhibitor of mitochondrial oxidative phosphorylation.NMS-873 作为一种线粒体氧化磷酸化的双重抑制剂。
Biochimie. 2021 Jun;185:33-42. doi: 10.1016/j.biochi.2021.03.004. Epub 2021 Mar 13.
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CFTR/ENaC-dependent regulation of membrane potential during human sperm capacitation is initiated by bicarbonate uptake through NBC.CFTR/ENaC 依赖性调节人精子获能期间的膜电位是通过 NBC 摄取碳酸氢根启动的。
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The involvement of endoplasmic reticulum formation and protein synthesis efficiency in VCP- and ATL1-related neurological disorders.内质网形成和蛋白质合成效率在 VCP 和 ATL1 相关神经疾病中的作用。
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