Intercellular adhesion molecule-1 is a regulator of blood-testis barrier function

J Cell Sci. 2012 Dec 1;125(Pt 23):5677-89. doi: 10.1242/jcs.107987. Epub 2012 Sep 12.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Blood-Testis Barrier / metabolism*
  • Cells, Cultured
  • Female
  • Immunoblotting
  • Immunohistochemistry
  • Immunoprecipitation
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Male
  • Microscopy, Confocal
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Sertoli Cells / metabolism
  • Testis / metabolism*
  • Tight Junctions / metabolism*

Substances

  • Antigens, CD
  • Intercellular Adhesion Molecule-1