Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel regulator of cell adhesion and the blood-testis barrier integrity in the seminiferous epithelium

FASEB J. 2009 Aug;23(8):2555-67. doi: 10.1096/fj.06-070573. Epub 2009 Mar 17.


In the seminiferous epithelium, Eps8 is localized to actin-based cell junctions at the blood-testis barrier (BTB) and the apical ectoplasmic specialization (ES) in stage V-VI tubules but is considerably diminished in stage VIII tubules. Eps8 down-regulation coincides with the time of BTB restructuring and apical ES disassembly, implicating the role of Eps8 in cell adhesion. Its involvement in Sertoli-germ cell adhesion was substantiated in studies using an in vivo animal model by treating rats with 1-(2,4-dichlorobenzy)-1H-indazole-3-carbohydrazide (adjudin) to induce anchoring junction restructuring, during which Eps8 disappeared at the apical ES before germ cell departure. In Sertoli cell cultures with established permeability barrier mimicking the BTB in vivo, the knockdown of Eps8 by RNAi led to F-actin disorganization and the mislocalization of the tight junction proteins occludin and ZO-1, suggesting the function of Eps8 in maintaining BTB integrity. In vivo knockdown of Eps8 in the testis caused germ cell sloughing and BTB damage, concomitant with occludin mislocalization, further validating that Eps8 is a novel regulator of cell adhesion and BTB integrity in the seminiferous epithelium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing
  • Adherens Junctions / drug effects
  • Adherens Junctions / metabolism
  • Animals
  • Base Sequence
  • Blood-Testis Barrier / drug effects
  • Blood-Testis Barrier / physiology*
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cells, Cultured
  • DNA Primers / genetics
  • Hydrazines / pharmacology
  • Indazoles / pharmacology
  • Male
  • Proteins / antagonists & inhibitors
  • Proteins / genetics
  • Proteins / physiology*
  • RNA Interference
  • Rats
  • Rats, Sprague-Dawley
  • Seminiferous Epithelium / cytology*
  • Seminiferous Epithelium / drug effects
  • Seminiferous Epithelium / physiology*
  • Sertoli Cells / cytology
  • Sertoli Cells / drug effects
  • Sertoli Cells / physiology
  • Spermatids / cytology
  • Spermatids / drug effects
  • Spermatids / physiology
  • Spermatogenesis / physiology


  • 1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide
  • Actins
  • Adaptor Proteins, Signal Transducing
  • DNA Primers
  • Eps8 protein, rat
  • Hydrazines
  • Indazoles
  • Proteins