14-3-3 Protein regulates cell adhesion in the seminiferous epithelium of rat testes

Endocrinology. 2009 Oct;150(10):4713-23. doi: 10.1210/en.2009-0427. Epub 2009 Jul 16.


Polarity proteins have been implicated in regulating and maintaining tight junction (TJ) and cell polarity in epithelia. Here we report 14-3-3theta, the homolog of Caenorhabditis elegans Par5 in mammalian cells, which is known to confer cell polarity at TJ, is found at the apical ectoplasmic specialization (ES), a testis-specific adherens junction type restricted to the Sertoli cell-elongating spermatid interface, in which TJ is absent. 14-3-3theta was shown to play a critical role in conferring cell adhesion at the apical ES. A loss of 14-3-3theta expression at the apical ES was detected in the seminiferous epithelium before spermiation. Involvement of 14-3-3theta in Sertoli cell adhesion was confirmed by its knockdown by RNA interference in Sertoli cells cultured in vitro with established TJ permeability barrier that mimicked the blood-testis barrier (BTB) in vivo. Mislocalization of N-cadherin and zonula occludens-1, but not alpha- and beta-catenins, was observed after 14-3-3theta knockdown in Sertoli cells, moving from the cell-cell interface to cytosol, indicating a disruption of cell adhesion. Studies by endocytosis assay illustrated that this loss of cell adhesion was mediated by an increase in the kinetics of endocytosis of N-cadherin and junctional adhesion molecule-A at the BTB, which may represent a general mechanism by which polarity proteins regulate cell adhesion. In summary, the testis is using 14-3-3theta to regulate cell adhesion at the apical ES to facilitate spermiation and at the BTB to facilitate the transit of preleptotene spermatocytes at stages VIII-IX of the epithelial cycle. 14-3-3theta may act as a molecular switch that coordinates these two cellular events in the seminiferous epithelium during spermatogenesis.

Publication types

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

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Blood-Testis Barrier / physiology*
  • Carrier Proteins / metabolism
  • Cell Adhesion*
  • Endocytosis*
  • Gene Knockdown Techniques
  • Hydrazines
  • Indazoles
  • Male
  • Rats
  • Seminiferous Epithelium / physiology*
  • Sertoli Cells / physiology
  • Spermatids / physiology
  • Tight Junctions / physiology


  • 1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide
  • 14-3-3 Proteins
  • Actins
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Hydrazines
  • Indazoles
  • Pard6a protein, rat