CABYR is essential for fibrous sheath integrity and progressive motility in mouse spermatozoa

J Cell Sci. 2016 Dec 1;129(23):4379-4387. doi: 10.1242/jcs.193151. Epub 2016 Oct 19.

Abstract

Ca2+-binding tyrosine-phosphorylation-regulated protein (CABYR) has been implicated in sperm physiological function in several in vitro studies. It has also been implicated as a potential cause of and diagnostic tool in asthenozoospermic human males. CABYR is known to be localized to the fibrous sheath, an accessory structure in the flagellar principal piece. Utilizing the CRISPR-Cas9 technology, we have knocked out this gene in mice to understand its role in male fertility. Cabyr-knockout male mice showed severe subfertility with a defect in sperm motility as well as a significant disorganization in the fibrous sheath. Further, abnormal configuration of doublet microtubules was observed in the Cabyr-knockout spermatozoa, suggesting that the fibrous sheath is important for the correct organization of the axoneme. Our results show that it is the role of CABYR in the formation of the fibrous sheath that is essential for male fertility.

Keywords: CABYR; CRISPR–Cas9; Fibrous sheath; Knockout; Spermatozoa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CRISPR-Cas Systems / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Epididymis / metabolism
  • Epididymis / ultrastructure
  • Female
  • Fertility
  • Gene Deletion
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Knockout
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Isoforms / metabolism
  • Reproducibility of Results
  • Sperm Motility / physiology*
  • Spermatozoa / metabolism*
  • Spermatozoa / ultrastructure
  • Substrate Specificity
  • Tyrosine / metabolism

Substances

  • Cabyr protein, mouse
  • Calcium-Binding Proteins
  • Phosphoproteins
  • Protein Isoforms
  • Tyrosine
  • Cyclic AMP-Dependent Protein Kinases