LINCking the Nuclear Envelope to Sperm Architecture

Francesco Manfrevola,Silvia Fasano,Riccardo Pierantoni,Florian Guillou,Rosanna Chianese

doi:10.3390/genes12050658

Abstract

Nuclear architecture undergoes an extensive remodeling during spermatogenesis, especially at levels of spermatocytes (SPC) and spermatids (SPT). Interestingly, typical events of spermiogenesis, such as nuclear elongation, acrosome biogenesis, and flagellum formation, need a functional cooperation between proteins of the nuclear envelope and acroplaxome/manchette structures. In addition, nuclear envelope plays a key role in chromosome distribution. In this scenario, special attention has been focused on the LINC (linker of nucleoskeleton and cytoskeleton) complex, a nuclear envelope-bridge structure involved in the connection of the nucleoskeleton to the cytoskeleton, governing mechanotransduction. It includes two integral proteins: KASH- and SUN-domain proteins, on the outer (ONM) and inner (INM) nuclear membrane, respectively. The LINC complex is involved in several functions fundamental to the correct development of sperm cells such as head formation and head to tail connection, and, therefore, it seems to be important in determining male fertility. This review provides a global overview of the main LINC complex components, with a special attention to their subcellular localization in sperm cells, their roles in the regulation of sperm morphological maturation, and, lastly, LINC complex alterations associated to male infertility.

Highlights

Spermatogenesis is a differentiation process, spatio-temporally coordinated, responsible for spermatozoa (SPZ) production [1,2]
The nuclear structure undergoes a dynamic remodeling to favor the meiotic pairing of the homologous chromosomes, their separation to form haploid cells, and, the extreme chromatin condensation in order to protect the paternal genome from chemical and physical insults and to reduce sperm head size, guaranteeing the hydrodynamic shape of SPZ [5,6,7]
Outer (ONM) and inner (INM) nuclear membranes, periodically fused at sites forming the nuclear pore complexes (NPCs), play different roles: ONM proteins are especially implicated in nuclear positioning and movement, while INM proteins are in close association with nuclear lamina and chromatin, regulating a wide range of nuclear functions such as DNA replication and transcription, chromatin organization, mitosis, and meiosis [10,11,12,13]

Summary

Introduction

Spermatogenesis is a differentiation process, spatio-temporally coordinated, responsible for spermatozoa (SPZ) production [1,2]. Male germ cells undergo three fundamental phases: (i) self-renewal of spermatogonial stem cells (SSC) and proliferation of spermatogonia (SPG); (ii) meiosis of spermatocytes (SPC) for haploid round spermatid (rSPT) production; and (iii) morphogenesis of rSPT into SPZ [3,4] During these events, the nuclear structure undergoes a dynamic remodeling to favor the meiotic pairing of the homologous chromosomes, their separation to form haploid cells, and, the extreme chromatin condensation in order to protect the paternal genome from chemical and physical insults and to reduce sperm head size, guaranteeing the hydrodynamic shape of SPZ [5,6,7]. In this scenario, focusing on sperm cells, we report a global overview of the main LINC complex components and their regulatory action in mechanotransduction, with a special attention paid to their subcellular localization in SPZ, their roles in the regulation of sperm morphological maturation, and, lastly, LINC complex alterations associated to male infertility

The Role of the LINC Complex in Mechanotransduction

Actin Functions in Sperm Head and Tail

A Special Focus

LINC Complex and Sperm Tail

LINC Complex and Male Infertility

Future Perspective