Differential phosphorylation of two serine clusters in mouse HORMAD1 during meiotic prophase I progression

Exp Cell Res. 2024 Jul 1;440(1):114133. doi: 10.1016/j.yexcr.2024.114133. Epub 2024 Jun 17.

Abstract

Mouse HORMAD1 is a phospho-protein involved in multiple functions during meiotic prophase I. To obtain insight into the significance of its phosphorylation, we generated phospho-specific antibodies against two serine residues, Ser307 and Ser378, representing each of two serine clusters in mouse HORMAD1. The Ser307 phosphorylation is detectable from early leptotene substage in both wild-type and Spo11-/- spermatocytes, indicating that Ser307 is a primary and SPO11-independent phosphorylation site. In contrast, the Ser378 phosphorylation is negligible at earlier substages in wild-type and Spo11-/- spermatocytes. After mid-zygotene substage, the Ser378 phosphorylation is abundant on unsynapsed chromosome axes in wild-type spermatocytes and is detected only in a part of unsynapsed chromosome axes in Spo11-/- spermatocytes. We also generated a non-phosphorylated Ser307-specific antibody and found that Ser307 is phosphorylated on sex chromosome axes but is almost entirely unphosphorylated on desynapsed chromosome axes in diplotene spermatocytes. These results demonstrated a substage-specific phosphorylation status of mouse HORMAD1, which might be associated with multiple substage-specific functions.

Keywords: HORMAD1; Meiotic substage; Phospho-specific antibody; Phosphorylation; Serine cluster.

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism
  • Male
  • Meiotic Prophase I*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • Serine* / metabolism
  • Sex Chromosomes / genetics
  • Sex Chromosomes / metabolism
  • Spermatocytes* / metabolism

Substances

  • Serine
  • Nohma protein, mouse
  • meiotic recombination protein SPO11
  • Endodeoxyribonucleases
  • Cell Cycle Proteins