Regulation of the blood-testis barrier by a local axis in the testis: role of laminin α2 in the basement membrane.
Laminin α2 is one of the constituent components of the basement membrane (BM) in adult rat testes. Earlier studies that used a mouse genetic model have shown that a deletion of laminin α2 impedes male fertility by disrupting ectoplasmic specialization (ES; a testis-specific, actin-rich anchoring junction) function along the length of Sertoli cell in the testis. This includes ES at the Sertoli cell-elongating/elongated spermatid interface, which is known as apical ES and possibly the Sertoli-Sertoli cell interface, known as basal ES, at the blood-testis barrier (BTB). Studies have also illustrated that there is a local regulatory axis that functionally links cellular events of spermiation that occur near the luminal edge of tubule lumen at the apical ES and the basal ES/BTB remodeling near the BM at opposite ends of the seminiferous epithelium during the epithelial cycle, known as the apical ES-BTB-BM axis. However, the precise role of BM in this axis remains unknown. Here, we show that laminin α2 in the BM serves as the crucial regulator in this axis as laminin α2, likely its 80-kDa fragment from the C terminus, was found to be transported across the seminiferous epithelium at stages VIII-IX of the epithelial cycle, from the BM to the luminal edge of the tubule, possibly being used to modulate apical ES restructuring at these stages. Of more importance, a knockdown of laminin α2 in Sertoli cells was shown to induce the Sertoli cell tight junction permeability barrier disruption via changes in localization of adhesion proteins at the tight junction and basal ES at the Sertoli cell BTB. These changes were found to be mediated by a disruption of F-actin organization that was induced by changes in the spatiotemporal expression of actin binding/regulatory proteins. Furthermore, laminin α2 knockdown also perturbed microtubule (MT) organization by considerable down-regulation of MT polymerization via changes in the spatiotemporal expression of EB1 (end-binding protein 1), a +TIP (MT plus-end tracking protein). In short, laminin α2 in the BM seems to play a crucial role in the BTB-BM axis by modulating BTB dynamics during spermatogenesis.-Gao, Y., Mruk, D., Chen, H., Lui, W.-Y., Lee, W. M., Cheng, C. Y. Regulation of the blood-testis barrier by a local axis in the testis: role of laminin α2 in the basement membrane.
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA.
Ying
Y
Gao
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA.
Dolores
D
Mruk
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA.
Haiqi
H
Chen
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Wing-Yee
WY
Lui
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Will M
WM
Lee
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; y-cheng@popcbr.rockefeller.edu.
C Yan
CY
Cheng
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D001814:Blood-Testis Barrier / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000187:drug effects / Q000502:physiology*; D050257:Tubulin Modulators / Q000494:pharmacology
D007797:Laminin; D050257:Tubulin Modulators; C102645:laminin alpha 2; D017239:Paclitaxel
Sertoli cell adhesion; ectoplasmic specialization; spermatid adhesion; spermatogenesis