The NEMP family supports metazoan fertility and nuclear envelope stiffness

Abstract
Human genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in NEMP1 (nuclear envelope membrane protein 1) with early menopause; however, it is unclear whether NEMP1 has any role in fertility. We show that whole-animal loss of NEMP1 homologs in Drosophila, Caenorhabditis elegans, zebrafish, and mice leads to sterility or early loss of fertility. Loss of Nemp leads to nuclear shaping defects, most prominently in the germ line. Biochemical, biophysical, and genetic studies reveal that NEMP proteins support the mechanical stiffness of the germline nuclear envelope via formation of a NEMP-EMERIN complex. These data indicate that the germline nuclear envelope has specialized mechanical properties and that NEMP proteins play essential and conserved roles in fertility.
Funding Information
  • National Institutes of Health (R01 GM100756)
  • National Institutes of Health
  • Genome Canada (OGI-097)
  • Ontario Genomics (OGI-139)
  • Canadian Institutes of Health Research (143319)
  • Canadian Institutes of Health Research (MOP-42462)
  • Canadian Institutes of Health Research (143301)
  • Krembil Foundation
  • Canadian Institutes of Health Research (167279)
  • Canadian Institutes of Health Research (PJT-148658)
  • Canada Research Chairs
  • Canadian Institutes of Health Research (156081)
  • Natural Sciences and Engineering Research Council of Canada
  • Natural Sciences and Engineering Research Council of Canada
  • Canadian Institutes of Health Research (MOP-102546)
  • Canadian Institutes of Health Research (MOP-130437)
  • Wellcome studentship
  • Canadian Institutes of Health Research (153128)
  • Wellcome Senior Research Fellowship (095209)