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<p>Centriolar satellites facilitate the delivery of proteins required for centrosome assembly and function, and rely on the nucleation of the scaffold protein pericentriolar material 1 (PCM1). During sperm maturation, centrosomes undergo remodeling to facilitate neckpiece formation and flagellogenesis. However, the role and mechanism of PCM1 in centrosome remodeling and sperm maturation remain to be elucidated. Herein we show that PCM1 is downregulated in patients with non-obstructive azoospermia. <i>Pcm1</i> knockout mice exhibit disrupted spermiogenesis, characterized by a disorganized manchette and head-tail coupling apparatus, defective flagellogenesis, and male infertility. Mechanistically, PCM1 binds centrosomal proteins and governs their precise translocation via intra-manchette transport, ensuring proper centrosome remodeling and axoneme biogenesis. Inactivation of PCM1 in sperm leads to severe retardation of embryo development, which cannot be overcome by intra-cytoplasmic sperm injection. Collectively, these findings establish PCM1 as a key regulator of spermatogenesis and spermiogenesis, highlighting the contribution of sperm centrosome-related proteins to embryo development and fertility.</p>

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PCM1 orchestrates centrosomal and flagellar protein transport to promote sperm maturation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月7日

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  • Zicong Huang,
  • Runduan Yi,
  • Xixian Cen,
  • Hanbin Zhang,
  • Minyu Xie,
  • Ke Ma,
  • Shipeng Ruan,
  • Yuge Zhuang,
  • Xiaoyuan Zhang,
  • Wenyuan Liu,
  • Hongrui Feng,
  • Deyu Chen,
  • Mohamed Morsi M. Ahmed,
  • Hong Liu,
  • Chuyu Huang,
  • Xiangjin Kang,
  • Zhenguo Chen

摘要

Centriolar satellites facilitate the delivery of proteins required for centrosome assembly and function, and rely on the nucleation of the scaffold protein pericentriolar material 1 (PCM1). During sperm maturation, centrosomes undergo remodeling to facilitate neckpiece formation and flagellogenesis. However, the role and mechanism of PCM1 in centrosome remodeling and sperm maturation remain to be elucidated. Herein we show that PCM1 is downregulated in patients with non-obstructive azoospermia. Pcm1 knockout mice exhibit disrupted spermiogenesis, characterized by a disorganized manchette and head-tail coupling apparatus, defective flagellogenesis, and male infertility. Mechanistically, PCM1 binds centrosomal proteins and governs their precise translocation via intra-manchette transport, ensuring proper centrosome remodeling and axoneme biogenesis. Inactivation of PCM1 in sperm leads to severe retardation of embryo development, which cannot be overcome by intra-cytoplasmic sperm injection. Collectively, these findings establish PCM1 as a key regulator of spermatogenesis and spermiogenesis, highlighting the contribution of sperm centrosome-related proteins to embryo development and fertility.