Focal adhesion kinase is a blood-testis barrier regulator

Autor(es)

Siu, Erica R. ^[1] ; Wong, Elissa W. P. ^[1] ; Mruk, Dolores D. ^[1] ; Porto, Catarina S. ^[2] ; Cheng, C. Yan ^[1]

Afiliação do(s) autor(es)

^[1] Populat Council, Ctr Biomed Res, New York, NY 10065 - USA

^[2] Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, BR-04044020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 106, n. 23, p. 9298-9303, JUN 9 2009.
• Citações Web of Science: 69

Resumo

In mammalian testes, such as rats, the mechanism(s) that regulate blood-testis barrier (BTB) restructuring at stages VIII-IX of the seminiferous epithelial cycle of spermatogenesis to facilitate the transit of preleptotene/leptotene spermatocytes is not known. This is due to the lack of information on the regulatory proteins at the BTB. Herein, focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, is shown to structurally interact with occludin and ZO-1 to form a functional protein complex at the BTB. Its expression at the BTB in the seminiferous epithelium is stage specific, being lowest at stage VIII-IX tubules, analogous to the expression pattern of occludin. Using primary Sertoli cells cultured in vitro with an established tight junction (TJ) permeability barrier that mimics the BTB in vivo, the knockdown of FAK by RNAi led to a transient disruption of the TJ barrier. This was accompanied by a loss of association between occludin and ZO-1, likely the result of reduced occludin phosphorylation at Tyr and Ser residues, but not Thr, which in turn led to a redistribution of occludin at the Sertoli-Sertoli cell interface, moving from cell membrane into cell cytosol, thereby disrupting the BTB. These findings suggest that a similar mechanism is in place in the testis in vivo to regulate BTB restructuring to facilitate the transit of primary spermatocytes. Furthermore, FAK was shown to be a molecular target of cadmium because its knockdown would desensitize Sertoli cells to cadmium-induced TJ barrier disruption. In summary, FAK is a unique regulator of BTB dynamics in the testis. (AU)

• Processo FAPESP: 06/51281-6 - Caracterizacao, funcao e vias de sinalizacao de receptores muscarinicos e receptores de estrogeno em espermatozoides de ratos.
• Beneficiário: Erica Rosanna Siu
• Modalidade de apoio: Bolsas no Brasil - Doutorado