Title

Blood-testis barrier dynamics are regulated by an engagement/disengagement mechanism between tight and adherens junctions via peripheral adaptors

Document Type

Article (peer-reviewed)

Publication Date

2005

Abstract

In the mammalian testis, the blood-testis barrier (BTB), unlike the blood-brain and blood-retina barriers, is composed of coexisting tight junctions (TJs) and adherens junctions (AJs). Yet these junctions must open (or disassemble) to accommodate the migration of preleptotene and leptotene spermatocytes across the BTB during spermatogenesis while maintaining its integrity. In this report, we show that the BTB utilizes a unique "engagement" and "disengagement" mechanism to permit the disruption of AJ that facilitates germ cell movement without compromising the BTB integrity. For instance, both TJ (e.g., occludin and JAM-1) and AJ (e.g., N-cadherin) integral membrane proteins were colocalized to the same site at the BTB. Although these TJ- and AJ-integral membrane proteins did not physically interact with each other, they were structurally linked by means of peripheral adaptors (e.g., ZO-1 and α- and γ-catenins). As such, these proteins are structurally "engaged" under physiological conditions to reinforce the BTB. When rats were exposed to Adjudin to induce AJ restructuring that eventually led to germ cell loss from the epithelium, this structural interaction between occludin and N-cadherin by means of their adaptors became "disengaged" while their protein levels were significantly induced. In short, when the epithelium is under assault, such as by Adjudin or plausibly at the time of germ cell migration across the BTB during spermatogenesis, the TJ- and AJ-integral membrane proteins can be disengaged. Thus, this mechanism is used by the testis to facilitate AJ restructuring to accommodate germ cell migration while maintaining the BTB integrity.

DOI

10.1073/pnas.0503855102

Language

English

Project

The Biology of Blood–Testis Barrier Dynamics

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