Work

Rictor/mTORC2 regulates blood‐testis barrier dynamics via its effects on gap junction communications and actin filament network

Year: 2013

Type: article

Abstract: In the mammalian testis, coexisting tight junctions (TJs), basal ectoplasmic specializations, and gap junctions (GJs), together with desmosomes near the basement membrane, constitute the blood-testis barrier (BTB). The most notable feature of the BTB, however, is the extensive network of actin filament bundles, which makes it one of the tightest blood-tissue barriers. The BTB undergoes restructuring to facilitate the transit of preleptotene spermatocytes at stage VIII-IX of the epithelial cycle. Thus, the F-actin network at the BTB undergoes cyclic reorganization via a yet-to-be explored mechanism. Rictor, the key component of mTORC2 that is known to regulate actin cytoskeleton, was shown to express stage-specifically at the BTB in the seminiferous epithelium. Its expression was down-regulated at the BTB in stage VIII-IX tubules, coinciding with BTB restructuring at these stages. Using an in vivo model, a down-regulation of rictor at the BTB was also detected during adjudin-induced BTB disruption, illustrating rictor expression is positively correlated with the status of the BTB integrity. Indeed, the knockdown of rictor by RNAi was found to perturb the Sertoli cell TJ-barrier function in vitro and the BTB integrity in vivo. This loss of barrier function was accompanied by changes in F-actin organization at the Sertoli cell BTB in vitro and in vivo, associated with a loss of interaction between actin and α-catenin or ZO-1. Rictor knockdown by RNAi was also found to impede Sertoli cell-cell GJ communication, disrupting protein distribution (e.g., occludin, ZO-1) at the BTB, illustrating that rictor is a crucial BTB regulator.

Source: The FASEB Journal

DOI: 10.1096/fj.12-212977

Authors: Ka‐Wai Mok, Dolores D. Mruk, Will M. Lee, C. Yan Cheng

Institutions: Population Council, University of Hong Kong

Language: English

Topic: Sperm and Testicular Function

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development