Abstract
Flagella and cilia are evolutionarily conserved cellular organelles. Abnormal formation or motility of these organelles in humans causes several syndromic diseases termed ciliopathies. The central component of flagella and cilia is the axoneme that is composed of the ‘9+2’ microtubule arrangement, dynein arms, radial spokes, and the Nexin-Dynein Regulatory Complex (N-DRC). The N-DRC is localized between doublet microtubules and has been extensively studied in the unicellular flagellate Chlamydomonas. Recently, it has been reported that TCTE1 (DRC5), a component of the N-DRC, is essential for proper sperm motility and male fertility in mice. Further, TCTE1 has been shown to interact with FBXL13 (DRC6) and DRC7; however, functional roles of FBXL13 and DRC7 in mammals have not been elucidated. Here we show that Fbxl13 and Drc7 expression are testes-enriched in mice. Although Fbxl13 knockout (KO) mice did not show any obvious phenotypes, Drc7 KO male mice were infertile due to their short immotile spermatozoa. In Drc7 KO spermatids, the axoneme is disorganized and the ‘9+2’ microtubule arrangement was difficult to detect. Further, other N-DRC components fail to incorporate into the flagellum without DRC7. These results indicate that Drc7, but not Fbxl13, is essential for the correct assembly of the N-DRC and flagella.
Highlights
Cilia and flagella are evolutionarily-conserved microtubule-based organelles extending from the surface of many cell types and are used for sensing and motility [1,2,3]
We focused on DRC3, GAS8, and TCTE1 because these DRCs were shown to be localized adjacent to DRC7 in Chlamydomonas flagella (Fig 1A) [13,14,15]
DRC7 is essential for male fertility at comparable levels. (B) Immunostaining of DRC3 and GAS8 in spermatozoa
Summary
Cilia and flagella are evolutionarily-conserved microtubule-based organelles extending from the surface of many cell types and are used for sensing and motility [1,2,3]. The central component of motile cilia and flagella is the axoneme, the ‘9+2’ microtubule arrangement that consists of a central pair (CP) of two singlet microtubules surrounded by nine outer microtubule doublets (Fig 1A) [5,6]. In addition to the microtubule arrangement, the axoneme contains several accessory structures such as inner dynein arms (IDAs), outer dynein arms (ODAs), radial spokes (RSs), and the Nexin-Dynein Regulatory Complex (N-DRC). The IDAs and ODAs are motor complexes attached to the A-tubule and drive axoneme beating by sliding the neighboring doublet microtubules in an ATP dependent manner [7,8]. The RSs extend from the doublet microtubules towards the CP and mediate signal transduction between the CP and the dynein arms [9]
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