The NEMP family supports metazoan fertility and nuclear envelope stiffness

Sci Adv. 2020 Aug 28;6(35):eabb4591. doi: 10.1126/sciadv.abb4591.

Yonit Tsatskis ¹, Robyn Rosenfeld ¹ ², Joel D Pearson ¹, Curtis Boswell ² ³, Yi Qu ¹, Kyunga Kim ¹ ⁴, Lacramioara Fabian ⁵, Ariz Mohammad ⁶, Xian Wang ⁷ ⁸, Michael I Robson ⁹, Karen Krchma ¹⁰, Jun Wu ¹⁰, João Gonçalves ¹, Didier Hodzic ¹¹, Shu Wu ¹, Daniel Potter ¹¹, Laurence Pelletier ¹ ², Wade H Dunham ¹, Anne-Claude Gingras ¹ ², Yu Sun ⁷ ⁸, Jin Meng ¹², Dorothea Godt ¹², Tim Schedl ⁶, Brian Ciruna ² ³, Kyunghee Choi ¹⁰ ¹³, John R B Perry ¹⁴, Rod Bremner ¹ ¹⁵, Eric C Schirmer ⁹, Julie A Brill ² ¹⁶, Andrea Jurisicova ¹ ⁴ ¹⁷, Helen McNeill ¹ ² ¹¹

Affiliations

1 Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada.
2 Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
3 Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
4 Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
5 Genome and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
6 Department of Genetics, School of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
7 Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada.
8 Institute of Biomaterials and Biomedical, University of Toronto, Toronto, ON M5S 3G9, Canada.
9 Wellcome Centre for Cell Biology and Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
10 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
11 Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
12 Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
13 Graduate School of Biotechnology, Kyung Hee University, Yong In, South Korea.
14 MRC Epidemiology Unit, Cambridge Biomedical Campus, University of Cambridge School of Clinical Medicine, Cambridge, UK.
15 Departments of Ophthalmology and Visual Science and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
16 Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
17 Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON M5G 1E2, Canada.

PMID: 32923640 DOI: 10.1126/sciadv.abb4591

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.

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