Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons

Abstract

The blood-testis barrier (BTB) is an important ultrastructure in the testis that supports meiosis and postmeiotic spermatid development since a delay in the establishment of a functional Sertoli cell barrier during postnatal development in rats or mice by 17–20 day postpartum (dpp) would lead to a delay of the first wave of meiosis. Furthermore, irreversible disruption of the BTB by toxicants also induces infertility in rodents. Herein, we summarize recent findings that BTB dynamics (i.e., disassembly, reassembly, and stabilization) are supported by the concerted efforts of the actin- and microtubule (MT)-based cytoskeletons. We focus on the role of two actin nucleation protein complexes, namely, the Arp2/3 (actin-related protein 2/3) complex and formin 1 (or the formin 1/spire 1 complex) known to induce actin nucleation, respectively, by conferring plasticity to actin cytoskeleton. We also focus on the MT plus (+)-end tracking protein (+TIP) EB1 (end-binding protein 1) which is known to confer MT stabilization. Furthermore, we discuss in particular how the interactions of these proteins modulate BTB dynamics during spermatogenesis. These findings also yield a novel hypothetical concept regarding the molecular mechanism that modulates BTB function.

Importance of the Androgen Receptor Signaling in Gene Transactivation and Transrepression for Pubertal Maturation of the Testis

“…Therefore, the morphological changes that Sertoli cells undergo as part of their maturation process reflect the changes that germ cells in direct contact with them undergo as well. A key player in this mutual maturation process is the Sertoli cell cytoskeleton, mainly formed by microtubules, actin filaments and vimentin intermediate filaments [23,24,25,26,27].…”

Growth kinetics of Chlamydia trachomatis in primary human Sertoli cells

“…In fact, by analysing the subcellular localization and integrity of the main components of cell cytoskeleton, namely F-Actin fibres, Vimentin-based intermediate filaments and α-tubulin microtubules, we observed that the development of a C. trachomatis inclusion into a human Sertoli cell led to alteration in its cytoskeleton. Recent studies have shown that actin and microtubule-based cytoskeleton in Sertoli cells plays a crucial role to preserve the homeostasis of the BTB 20 . Our observation that Vimentin-based intermediate filaments and α-tubulin microtubules were re-organized in thick fibres surrounding the chlamydial inclusion, hints at the intriguing possibility that C. trachomatis might adversely affect the integrity of the BTB, and, hence, impair the spermatogenesis.…”

“…To accommodate the entry of spermatocytes into the adluminal compartment, existing junctions above them must transiently disassemble, leading to changes in protein-protein interactions 17 . The restructuring of the BTB is a complex process that is mainly supported by the Sertoli cell cytoskeleton, and, as such, the maintenance of its structural integrity is essential for the generation of mature functional spermatozoa 17,19,20 .…”

Muscarinic Acetylcholine Receptor M5 Involved in Spermatogenesis through the Modification of Cell-Cell Junctions

“…ES includes basal ES at the Sertoli cell-cell interface of the BTB, and the apical ES at the Sertoli-spermatid interface (Li et al, 2015). Actin-based cytoskeletons in Sertoli and germ cells play crucial roles in the regulation of homeostasis of the BTB and the cytoskeletal elements at the basal ES (Wen et al, 2018c). Even though there have been many recent reports that have highlighted the factors involved in the regulation of the BTB and ES (Wen et al, 2018;Li et al, 2015), the intriguing cross-talk mechanism(s) between basal and apical ES are still not fully understood, because the restructuring of the BTB close to the basement membrane and the disruption of the apical tubulobulbar complex (TBC) at the luminal edge of the epithelium happen almost concurrently (Li et al, 2015).…”