Ectoplasmic specialization: a friend or a foe of spermatogenesis?

Abstract

The ectoplasmic specialization (ES) is a testis-specific, actin-based hybrid anchoring and tight junction. It is confined to the interface between Sertoli cells at the blood-testis barrier, known as the basal ES, as well as between Sertoli cells and developing spermatids designated the apical ES. The ES shares features of adherens junctions, tight junctions and focal contacts. By adopting the best features of each junction type, this hybrid nature of ES facilitates the extensive junction-restructuring events in the seminiferous epithelium during spermatogenesis. For instance, the alpha6beta1-integrin-laminin 333 complex, which is usually limited to the cell-matrix interface in other epithelia to facilitate cell movement, is a putative apical ES constituent. Furthermore, JAM-C and CAR, two tight junction integral membrane proteins, are also components of apical ES involving in spermatid orientation. We discuss herein the mechanisms that maintain the cross-talk between ES and blood-testis barrier to facilitate cell movement and orientation in the seminiferous epithelium.

Figure 1

A schematic drawing to show the hybrid property of apical ES having the characteristics of AJ, FAC and TJ. The drawing illustrates the relative locations of junctions between Sertoli cells, Sertoli–germ cells and Sertoli cells–extracellular matrix (ECM) as well as different stages of germ-cell development in the seminiferous epithelium of adult rat testes (top panel). Hemidesmosomes is a cell–matrix intermediate filament based anchoring junction with α6β4-integrin as the transmembrane receptor (bottom left panel). This anchoring junction is important for Sertoli cells to anchor onto the basement membrane. However, there is no direct evidence for the presence of α6β4-integrin in the testis. The existence of focal adhesion complex between Sertoli cells and ECM in the rat testis is not well-defined. The bottom right panel is the molecular architecture of apical ES in the seminiferous epithelium. Apical ES is a hybrid AJ (e.g. cadherins/catenins, nectins/afadin), focal contact anchoring junction (e.g. integrins/laminins) and TJ (e.g. JAM-C, CAR). This model was prepared based on recent findings in the field (see text).

Figure 2

A schematic drawing illustrating the mechanism of spermatid movement along Sertoli cells in the seminiferous epithelium via a cascade of biological events. Spermiation occurs at stage VIII of the epithelial cycle, which coincides with the time for the passage of preleptoene spermatocytes (PS) across the BTB. During these cellular events, the different cascades of biological events (see the numbers in the figure) happen in a highly regulated manner. We hypothesize that germ cell movement involves the continuous disassembly and reassembly of Sertoli–Sertoli and Sertoli–germ cell junctions. These require the presence of cytokines (e.g. TNFα and TGF-β3) and proteases to perturb the junctions by lowering the steady-state protein level of several integral TJ and AJ proteins. Protein kinases and protein phosphatases also mediate tyrosine phosphorylation of the AJ (cadherin/catenin/CK2/cSrc) and FAC-like (integrin/laminin/FAK/cSrc) adhesion complex or an induction of cofilin and/or gelsolin. The net result of these changes leads to a weakening of adhesion complexes at the basal and apical ES. A transient disengagement between TJ and AJ via peripheral adaptors, such as ZO-1 and catenins, is used to preserve the BTB integrity when AJ is perturbed. To assist spermatid movement, upward traction force is generated by the motor proteins, such as myosin VIIa and dynein, at both the apical and basal ES, involving GTPases. Prior to spermiation, integral membrane junction proteins such as nectin-2 and nectin-3 may be internalized by both apical and basal TBC to facilitate the depletion of elongate spermatid (ES) from the epithelium (i.e. spermiation) and the passage of PS across the BTB. Recently, it has been speculated that cleavage of laminin at the apical ES by MMPs can assist the ‘opening’ of BTB via a yet-to-be identified signaling pathway. This model was prepared based on recent findings in the field (see text). SC Nucleus, Sertoli cell nucleus.