p-FAK-Tyr397 regulates spermatid adhesion in the rat testis via its effects on F-actin organization at the ectoplasmic specialization

Hin Ting Wan, Dolores D. Mruk, Stephen Y.T. Li, Ka Wai Mok, Will M. Lee, Chris K C WONG, C. Yan Cheng

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

During spermatogenesis, the molecular mechanism that confers spermatid adhesion to the Sertoli cell at the apical ectoplasmic specialization (apical ES), a testis-specific F-actin-rich adherens junction, in the rat testis remains elusive. Herein, the activated form of focal adhesion kinase (FAK), p-FAK-Tyr397, a component of the apical ES that was expressed predominantly and stage specifically in stage VII-early stage VIII tubules, was found to be a crucial apical ES regulator. Using an FAK-Y397E phosphomimetic mutant cloned in a mammalian expression vector for its transfection vs. FAK and vector alone in adult rat testes in vivo, its overexpression was found to cause defects in spermiation. These defects in spermiation were manifested by entrapment of spermatids in the seminiferous epithelium in late stage VIII-X tubules and were mediated by a disruption on the spatiotemporal expression and/or mislocalization of actin regulatory protein actin-related protein 3, which induces branched actin polymerization, epidermal growth factor receptor pathway substrate 8 (an actin barbed end capping and bundling protein), and palladin (an actin cross-linking and bundling protein). This thus perturbed changes of F-actin organization at the apical ES to facilitate spermiation, which also led to a concomitant alteration in the distribution and upregulation of adhesion proteins nectin-2 and nectin-3 at the apical ES. As such, nectin-2 and -3 remained at the apical ES to anchor step 19 spermatids on to the epithelium, delaying spermiation. These findings illustrate a mechanistic pathway mediated by p-FAK-Tyr397 that regulates spermatid adhesion at the apical ES in vivo.

Original languageEnglish
Pages (from-to)E687-E699
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume305
Issue number6
DOIs
Publication statusPublished - Sep 2013

Scopus Subject Areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

User-Defined Keywords

  • Actin filament bundles
  • Adherens junction
  • Focal adhesion kinase
  • Focal adhesion kinase mutant
  • Spermatogenesis
  • Testis

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