Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice

J Cell Sci. 2018 Oct 8;131(19):jcs221481. doi: 10.1242/jcs.221481.

Abstract

Chemokines are signaling proteins that are secreted to induce chemotaxis during an immunological response. However, the functions of transmembrane-type chemokine-like factor (CKLF) and the CMTM (CKLF-like MARVEL transmembrane domain containing) protein family remain to be determined. In this study, we focused on the testis-specific mouse CMTM gene cluster (Cmtm1, Cmtm2a and Cmtm2b) and generated CRISPR/Cas9-mediated mutant mice to examine their physiological functions. Although Cmtm1 mutant mice were fertile, Cmtm2a and Cmtm2b double mutant mice had defects in male fertility due to impaired sperm function. We found that co-expression of sperm membrane proteins CMTM2A and CMTM2B is required for male fertility and affects the localization of the sperm membrane protein ADAM3 in regulating sperm fertilizing ability.

Keywords: CKLF; CMTM gene cluster; CRISPR/Cas9; Fertilization; Testis; Zona pellucida.

Publication types

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

MeSH terms

  • ADAM Proteins / metabolism*
  • Animals
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Fertility*
  • MARVEL Domain-Containing Proteins / genetics
  • MARVEL Domain-Containing Proteins / metabolism*
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice, Knockout
  • Mice, Mutant Strains
  • Multigene Family
  • Organ Specificity
  • Protein Binding
  • Protein Transport
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sperm Head / metabolism
  • Spermatozoa / metabolism*
  • Testis / metabolism

Substances

  • Chemokines
  • Cmtm2a protein, mouse
  • Cmtm2b protein, mouse
  • MARVEL Domain-Containing Proteins
  • Membrane Glycoproteins
  • Repressor Proteins
  • ADAM Proteins
  • Adam3 protein, mouse