TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa

Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5370-E5378. doi: 10.1073/pnas.1621279114. Epub 2017 Jun 19.

Abstract

Flagella and cilia are critical cellular organelles that provide a means for cells to sense and progress through their environment. The central component of flagella and cilia is the axoneme, which comprises the "9+2" microtubule arrangement, dynein arms, radial spokes, and the nexin-dynein regulatory complex (N-DRC). Failure to properly assemble components of the axoneme leads to defective flagella and in humans leads to a collection of diseases referred to as ciliopathies. Ciliopathies can manifest as severe syndromic diseases that affect lung and kidney function, central nervous system development, bone formation, visceral organ organization, and reproduction. T-Complex-Associated-Testis-Expressed 1 (TCTE1) is an evolutionarily conserved axonemal protein present from Chlamydomonas (DRC5) to mammals that localizes to the N-DRC. Here, we show that mouse TCTE1 is testis-enriched in its expression, with its mRNA appearing in early round spermatids and protein localized to the flagellum. TCTE1 is 498 aa in length with a leucine rich repeat domain at the C terminus and is present in eukaryotes containing a flagellum. Knockout of Tcte1 results in male sterility because Tcte1-null spermatozoa show aberrant motility. Although the axoneme is structurally normal in Tcte1 mutant spermatozoa, Tcte1-null sperm demonstrate a significant decrease of ATP, which is used by dynein motors to generate the bending force of the flagellum. These data provide a link to defining the molecular intricacies required for axoneme function, sperm motility, and male fertility.

Keywords: asthenozoospermia; glycolysis; male infertility; mutant mouse; testis-specific gene.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Axoneme / metabolism
  • Chlamydomonas / metabolism
  • Cilia / metabolism
  • Crosses, Genetic
  • Cytoskeleton / metabolism
  • Dyneins / metabolism*
  • Female
  • Flagella / metabolism
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Homozygote
  • Humans
  • Male
  • Mice
  • Microtubules / metabolism
  • Mutation
  • Proteins / genetics*
  • Proteins / physiology
  • Sperm Motility*
  • Spermatids / metabolism
  • Spermatozoa / physiology*
  • Testis / metabolism

Substances

  • Proteins
  • TCTE1 protein, mouse
  • Green Fluorescent Proteins
  • Adenosine Triphosphate
  • Dyneins