In the seminiferous epithelium of tubules, such as at stage VII as shown herein on the left panel, the BTB integrity is maintained through an up-regulation of the Par6- and CRB3-based polarity complexes (see Figure 4), likely involving actin bundling proteins (e.g., palladin, Eps8), to maintain the actin microfilament bundles to confer cell adhesive function since both TJ (e.g., occlduin-ZO-1)- and basal ES (N-cadherin-β-catenin)-protein complexes are utilizing F-actin for attachment. Scribble provides a unique mechanism to modulate BTB dynamics to support the transport of preleptotene spermatocytes across the immunological barrier at stage VIII of the epithelial cycle. Thus, the antagonistic effects of CRB3/Par6-based polarity complexes vs. Studies by RNAi to knockdown CRB3 and Par6 have shown to perturb the Sertoli cell TJ-permeability barrier whereas Scribble/Lgl2/Dlg1 triple knockdown promotes the Sertoli cell TJ-barrier function by making it tighter (see text for details), illustrating in normal testes, CRB3 and Par6 promotes the BTB integrity whereas Scribble promotes BTB restructuring/remodeling. In sharp contrast, Scribble (pink) is expressed at the BTB at all stages but at relatively low level except at stages VII-VIII when a considerable surge in expression is noted. CRB3 (green) is predominantly expressed at the BTB at stages IV-VII but considerably diminished at stage VIII whereas Par6 (orange) is strongly expressed at the BTB at all stages except stage VIII, illustrating these two polarity protein complexes may be working synergistically to regulate BTB dynamics since both polarity complexes are down-regulated at stage VIII of the cycle when preleptotene spermatocytes are being transported across the immunologically barrier. The curves show relative stage-specific expression levels of CRB3, Par6 and Scribble at the BTB. This in turn provides a unique mechanism to modulate junction remodeling in the testis to support germ cell transport across the epithelium in particular the BTB during the epithelial cycle of spermatogenesis.Īctin microfilaments Cell polarity Cytoskeleton Germ cells Meiosis Polarity proteins Sertoli cells Spermatids Spermatogenesis Spermiogenesis Testis.Ĭopyright © 2016 Elsevier Ltd.
We also propose a hypothetical model which illustrates the antagonistic effects of these polarity proteins. These findings also illustrate polarity proteins exert their effects through the actin-based cytoskeleton mediated by actin binding and regulatory proteins, which in turn modulate adhesion protein complexes at the cell-cell interface since TJ, basal ES and GJ utilize F-actin for attachment. Herein, we discuss latest findings regarding the role of different polarity protein complexes or modules and how these protein complexes are working in concert to modulate Sertoli cell and spermatid polarity. However, the involvement of polarity proteins in this unique cellular organization, in particular the underlying molecular mechanism(s) by which polarity proteins confer cellular polarity in the seminiferous epithelium is virtually unknown until recent years. Furthermore, the heads of elongating/elongated spermatids point toward the basement membrane with their elongating tails toward the tubule lumen. Within the epithelium, undifferentiated spermatogonia and preleptotene spermatocytes restrictively reside in the basal compartment whereas spermatocytes and post-meiotic spermatids reside in the adluminal compartment. The BTB, in turn, divides the epithelium into the basal and the adluminal (apical) compartments. On the other hand, tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific actin-rich anchoring junction), gap junction (GJ) and desmosome that constitute the blood-testis barrier (BTB) are also located near the basement membrane. For instance, Sertoli cell nuclei are found near the basement membrane. When the cross-section of a seminiferous tubule from an adult rat testes is examined microscopically, Sertoli cells and germ cells in the seminiferous epithelium are notably polarized cells.