Actin binding proteins in blood–testis barrier function

Abstract

Purpose of review This review examines the role of actin binding proteins (ABPs) on blood-testis barrier (BTB), an androgen-dependent ultrastructure in the testis, in particular their involvement on BTB remodeling during spermatogenesis. Recent findings The BTB divides the seminiferous epithelium into the basal and the adluminal compartments. The BTB is constituted by coexisting actin-based tight junction (TJ), basal ectoplasmic specialization (ES) and gap junction (GJ), as well as intermediate filament-based desmosome (DS) between Sertoli cells near the basement membrane. Junctions at the BTB undergo continuous remodeling to facilitate the transport of preleptotene spermatocytes residing in the basal compartment across the immunological barrier during spermatogenesis. Thus, meiosis I/II and post-meiotic spermatid development take place in the adluminal compartment behind the BTB. BTB remodeling also regulates exchanges of biomolecules between the two compartments. Since TJ, basal ES and GJ use F-actin for attachment, actin microfilaments rapidly convert between their bundled and unbundled/branched configuration to confer BTB remodeling. The events of actin re-organization are regulated by two major classes ABPs that confer actin microfilaments into bundled versus branched/unbundled configuration. Summary We provide a model on how ABPs regulate BTB remodeling, shedding new lights in unexplained male infertility, such as environmental toxicant-induced reproductive dysfunction.

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

“…Herein we discuss some recent findings based on studies of the following selected actin-binding/regulatory proteins in the testis and how these proteins work alone or in concert with others to modulate the organization of actin microfilaments, most notably at the ES to regulate (1) spermatid adhesion and transport and (2) BTB dynamics to facilitate the transport of preleptotene spermatocytes across the immunological barrier. Other regulatory proteins such as actin-bundling proteins plastin 3, Eps8, ezrin, and palladin and regulatory protein kinases (e.g., FAK, c-Src, c-Yes) pertinent to the regulation of spermatogenesis have recently been reviewed [14, 19], and thus, they are not being discussed herein to avoid redundancy. Instead, we focus on a group of actin nucleation proteins; however, these actin nucleation proteins are grouped into two types: one confers branched actin nucleation (e.g., the Arp2/3 complex), whereas the other type confers linear actin nucleation (e.g., formin 1 and Spire 1).…”

“…However, these two cytoskeletal networks are intimately associated structurally and functionally to support spermatogenesis [9, 19]. Interestingly, studies have shown that both cytoskeletal networks can be modulated by the same proteins.…”

“…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].…”

Functional importance of JMY expression by Sertoli cells in mediating mouse spermatogenesis

“…On the other hand, those located at the Sertoli-Sertoli cell interface are referred to as the basal ES, which usually coexists with tight junctions and gap junctions to constitute the BTB structure. Interestingly, germ cell transport as well as endocytic vesicle trafficking in Sertoli cells requires rapid reorganization of these microfilament bundles, so that they are efficiently converted from a “bundled” to “unbundled/branched” configuration (Li et al, 2015). Briefly, there is no doubt that irrespective of the type of actin bundle configuration, in all cases they support and maintain cell junction integrity.…”

Drebrin and Spermatogenesis

“…These proteins coordinate to regulate actin microfilament remodeling at the basal ES and apical ES via their stage-specific and spatiotemporal expression, which, in turn, facilitate the transport of preleptotene spermatocytes across the BTB and the transport of elongating spermatids across the adluminal compartment, respectively. The coordinated efforts of those actin regulatory proteins have recently been reviewed (Li et al 2015a; Cheng and Mruk 2015; Su et al 2013). Herein, we focus our discussion on drebrin, a family of proteins known to regulate the action of the Arp2/3 complex which is a barbed end nucleation protein that effectively induces branched actin polymerization, thereby converting actin microfilaments from a linear to a branched configuration.…”