D-Aspartate Upregulates DAAM1 Protein Levels in the Rat Testis and Induces Its Localization in Spermatogonia Nucleus

Biomolecules. 2020 Apr 28;10(5):677. doi: 10.3390/biom10050677.

Abstract

Cell differentiation during spermatogenesis requires a proper actin dynamic, regulated by several proteins, including formins. Disheveled-Associated-Activator of Morphogenesis1 (DAAM1) belongs to the formins and promotes actin polymerization. Our results showed that oral D-Aspartate (D-Asp) administration, an excitatory amino acid, increased DAAM1 protein levels in germ cells cytoplasm of rat testis. Interestingly, after the treatment, DAAM1 also localized in rat spermatogonia (SPG) and mouse GC-1 cells nuclei. We provided bioinformatic evidence that DAAM1 sequence has two predicted NLS, supporting its nuclear localization. The data also suggested a role of D-Asp in promoting DAAM1 shuttling to the nuclear compartment of those proliferative cells. In addition, the proliferative action induced by D-Asp is confirmed by the increased levels of PCNA, a protein expressed in the nucleus of cells in the S phase and p-H3, a histone crucial for chromatin condensation during mitosis and meiosis. In conclusion, we demonstrated, for the first time, an increased DAAM1 protein levels following D-Asp treatment in rat testis and also its localization in the nucleus of rat SPG and in mouse GC-1 cells. Our results suggest an assumed role for this formin as a regulator of actin dynamics in both cytoplasm and nuclei of the germ cells.

Keywords: D-Asp; DAAM1; cytoskeleton; formins; mitosis; nuclear actin; spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • D-Aspartic Acid / metabolism
  • D-Aspartic Acid / pharmacology*
  • Male
  • Nuclear Localization Signals
  • Rats
  • Rats, Wistar
  • Spermatogonia / drug effects
  • Spermatogonia / metabolism*
  • Testis / cytology
  • Testis / metabolism*
  • Up-Regulation

Substances

  • Cytoskeletal Proteins
  • Daam1 protein, rat
  • Nuclear Localization Signals
  • D-Aspartic Acid