PNAS, 30 October, 2023, DOI：https://doi.org/10.1073/pnas.2313787120

CAMSAP1 role in orchestrating structure and dynamics of manchette microtubule minus-ends impacts male fertility during spermiogenesis

Weichang Hu, Rui Zhang, Honglin Xu, Yuejia Li, Xiaojuan Yang, Zhengrong Zhou, Xiahe Huang, Yingchun Wang, Wei Ji, Fei Gao, and Wenxiang Meng

Abstract

The manchette is a crucial transient structure involved in sperm development, with its composition and regulation still not fully understood. This study focused on investigating the roles of CAMSAP1 and CAMSAP2, microtubule (MT) minus-end binding proteins, in regulating manchette MTs, spermiogenesis, and male fertility. The loss of CAMSAP1, but not CAMSAP2, disrupts the well-orchestrated process of spermiogenesis, leading to abnormal manchette elongation and delayed removal, resulting in deformed sperm nuclei and tails resembling oligoasthenozoospermia symptoms. We investigated the underlying molecular mechanisms by purifying manchette assemblies and comparing them through proteomic analysis, and results showed that the absence of CAMSAP1 disrupted the proper localization of key proteins (CEP170 and KIF2A) at the manchette minus end, compromising its structural integrity and hindering MT depolymerization. These findings highlight the significance of maintaining homeostasis in manchette MT minus-ends for shaping manchette morphology during late spermiogenesis, offering insights into the molecular mechanisms underlying infertility and sperm abnormalities.

Article link：https://www.pnas.org/doi/10.1073/pnas.2313787120