title: Intercellular adhesion molecule-1 is a regulator of blood-testis barrier function.
abstract: The mechanism underlying the movement of preleptotene/leptotene spermatocytes across the blood-testis barrier (BTB) during spermatogenesis is not well understood largely owing to the fact that the BTB, unlike most other blood-tissue barriers, is composed of several co-existing and co-functioning junction types. In the present study, we show that intercellular adhesion molecule-1 [ICAM-1, a Sertoli and germ cell adhesion protein having five immunoglobulin (Ig)-like domains, in addition to transmembrane and cytoplasmic domains] is a regulator of BTB integrity. Initial experiments showed ICAM-1 to co-immunoprecipitate and co-localize with tight junction and basal ectoplasmic specialization proteins such as occludin and N-cadherin, which contribute to BTB function. More importantly, overexpression of ICAM-1 in Sertoli cells in vitro enhanced barrier function when monitored by transepithelial electrical resistance measurements, illustrating that ICAM-1-mediated adhesion can promote BTB integrity. On the other hand, overexpression of a truncated form of ICAM-1 that consisted only of the five Ig-like domains (sICAM-1; this form of ICAM-1 is known to be secreted) elicited an opposite effect when Sertoli cell barrier function was found to be perturbed in vitro; in this case, sICAM-1 overexpression resulted in the downregulation of several BTB constituent proteins, which was probably mediated by Pyk2/p-Pyk2-Y402 and c-Src/p-Src-Y530. These findings were expanded to the in vivo level when BTB function was found to be disrupted following sICAM-1 overexpression. These data illustrate the existence of a unique mechanism in the mammalian testis where ICAM-1 can either positively or negatively regulate BTB function.
authors.affiliation: Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10065,  USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xiao
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001814:Blood-Testis Barrier / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism; D013737:Testis / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018799:Intercellular Adhesion Molecule-1