Regulation of blood–testis barrier by actin binding proteins and protein kinases

Abstract

The blood-testis barrier (BTB) is an important ultrastructure in the testis since the onset of spermatogenesis coincides with the establishment of a functional barrier in rodents and humans. It is also noted that a delay in the assembly of a functional BTB following treatment of neonatal rats with drugs such as diethylstilbestrol or adjudin also delays the first wave of spermiation. While the BTB is one of the tightest blood-tissue barriers, it undergoes extensive remodeling, in particular at stage VIII of the epithelial cycle to facilitate the transport of preleptotene spermatocytes connected in clones across the immunological barrier. Without this timely transport of preleptotene spermatocytes derived from type B spermatogonia, meiosis will be arrested, causing aspermatogenesis. Yet the biology and regulation of the BTB remains largely unexplored since the morphological studies in the 1970s. Recent studies, however, have shed new light on the biology of the BTB. Herein, we critically evaluate some of these findings, illustrating that the Sertoli cell BTB is regulated by actin binding proteins (ABPs), likely supported by non-receptor protein kinases, to modulate the organization of actin microfilament bundles at the site. Furthermore, microtubule (MT)-based cytoskeleton is also working in concert with the actin-based cytoskeleton to confer BTB dynamics. This timely review provides an update on the unique biology and regulation of the BTB based on the latest findings in the field, focusing on the role of ABPs and non-receptor protein kinases.

Vitamin C mitigates heat damage by reducing oxidative stress, inducing HSP expression in TM4 Sertoli cells

“…As a dynamic cell, Sertoli cells show dynamic changes in their microtubule patterns as germ cells progress through the various spermatogenic stages (Vogl & Guttman, 2008). In this process, BTB undergoes periodical reconstruction to facilitate spermiogenesis and spermiation (Li & Cheng, 2016). Microtubules are components of the cytoskeleton, it is the fundamental unit of the spindle that is required for mitotic and meiotic cell division (Helmke, Heald, & Wilbur, 2013).…”

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

“…The MT- and actin-based cytoskeletons are two distinctive cytoskeletal networks, supported by different binding and regulatory proteins in the testis [5, 8, 9, 20]. However, these two cytoskeletal networks are intimately associated structurally and functionally to support spermatogenesis [9, 19].…”

“…1c, d). This coordinated effort is necessary to support the timely transport of step 19 spermatids across the epithelium in stage VII–VIII tubules to prepare for their release at spermiation in stage VIII tubules [19, 20]. But they are also necessary to facilitate the timely remodeling of the BTB to support the transport of preleptotene spermatocytes across the immunological barrier at stage VIII of the epithelial cycle [15, 16].…”

Planar cell polarity (PCP) proteins and spermatogenesis

“…In the testis, BTB undergoes remodeling at stage VIII of the epithelial cycle during which the ‘old’ BTB above the preleptotene spermatocytes connected in clones undergoes gradual degeneration, which coincides with the gradual assembly of a ‘new’ barrier behind these spermatocytes (for a review, see [45]). Studies have shown that these events require extensive endocytic vesicle-mediated trafficking so that integral membrane proteins and their associated adaptors from the ‘old’ BTB site can be rapidly endocytosed and recycled to assemble the ‘new’ BTB to avoid exhausting the available cell junction proteins in the Sertoli cell (for a review, see [46]).…”