RRC ID 68914
Author Morohoshi A, Miyata H, Shimada K, Nozawa K, Matsumura T, Yanase R, Shiba K, Inaba K, Ikawa M.
Title Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice.
Journal PLoS Genet
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.
Volume 16(1)
Pages e1008585
Published 2020-1-1
DOI 10.1371/journal.pgen.1008585
PMID 31961863
PMC PMC6994161
MeSH Animals Axoneme / genetics Axoneme / metabolism Axoneme / pathology Dyneins / metabolism* Female Flagella / genetics* Flagella / metabolism Flagella / pathology HEK293 Cells Humans Infertility, Male / genetics* Male Mice Mice, Inbred C57BL Microtubule-Associated Proteins / metabolism* Spermatogenesis Spermatozoa / cytology Spermatozoa / metabolism* Spermatozoa / pathology
IF 5.175
DNA material pCAG-mDrc3-PA (RDB19240) pCAG-mGas8-PA (RDB19241) pCAG-mTcte1-PA (RDB19242) pCAG-mDrc7-FLAG (RDB19243)