N-wasp is required for structural integrity of the blood-testis barrier

PLoS Genet. 2014 Jun 26;10(6):e1004447. doi: 10.1371/journal.pgen.1004447. eCollection 2014 Jun.

Abstract

During spermatogenesis, the blood-testis barrier (BTB) segregates the adluminal (apical) and basal compartments in the seminiferous epithelium, thereby creating a privileged adluminal environment that allows post-meiotic spermatid development to proceed without interference of the host immune system. A key feature of the BTB is its continuous remodeling within the Sertoli cells, the major somatic component of the seminiferous epithelium. This remodeling is necessary to allow the transport of germ cells towards the seminiferous tubule interior, while maintaining intact barrier properties. Here we demonstrate that the actin nucleation promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) provides an essential function necessary for BTB restructuring, and for maintaining spermatogenesis. Our data suggests that the N-WASP-Arp2/3 actin polymerization machinery generates branched-actin arrays at an advanced stage of BTB remodeling. These arrays are proposed to mediate the restructuring process through endocytic recycling of BTB components. Disruption of N-WASP in Sertoli cells results in major structural abnormalities to the BTB, including mis-localization of critical junctional and cytoskeletal elements, and leads to disruption of barrier function. These impairments result in a complete arrest of spermatogenesis, underscoring the critical involvement of the somatic compartment of the seminiferous tubules in germ cell maturation.

Publication types

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

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics*
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Blood-Testis Barrier*
  • Male
  • Mice
  • Seminiferous Epithelium / metabolism
  • Sertoli Cells / metabolism
  • Spermatids / metabolism
  • Spermatocytes / growth & development
  • Spermatocytes / metabolism
  • Spermatogenesis / genetics*
  • Testis / metabolism
  • Wiskott-Aldrich Syndrome Protein, Neuronal / genetics*

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Wasl protein, mouse
  • Wiskott-Aldrich Syndrome Protein, Neuronal

Grant support

This work was supported by grants from the National Institutes of Health (NICHD, U54 HD029990, Project 5 to CYC.; R01 HD056034 to CYC.), The Hong Kong General Research Fund (HKU771513 to WML, HKBU261812 to CKCW) and by an Administral Anslat Foundation grant to BZS, who is an incumbent of the Hilda and Cecil Lewis Chair in Molecular Genetics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.