Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse

Dunleavy, Jessica E M; Okuda, Hidenobu; O’Connor, Anne E; Merriner, D. Jo; O’Donnell, Liza; Jamsai, Duangporn; Bergmann, Martin; O’Bryan, Moira K

doi:10.1371/journal.pgen.1007078

Cited by 56 publications

(83 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At the early steps of spermiogenesis, the axoneme composed of microtubules elongates and a transient microtubule structure called the manchette is assembled [36]. The manchette is involved in sperm head elongation, and abnormal head morphology is often related to defects in the formation, function, and movement of the manchette [37][38][39][40]. To observe the axoneme and manchette, we performed immunofluorescence using an anti-α-tubulin antibody on spermatogenic cells obtained from seminiferous tubules.…”

Section: Axoneme Formation and Manchette Removal Is Impaired In Drc7 mentioning

confidence: 99%

Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Axoneme Formation and Manchette Removal Is Impaired In Drc7 mentioning

confidence: 99%

Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Duolink proximity ligation assays (Duolink PLA) were performed according the manufacturer's instructions (Sigma-Aldrich) and our previous study [37]. Concisely, purified murine sperm were fixed on the slides, following incubation by Duolink blocking solution for 60 minutes at 37˚C.…”

Section: Duolink Proximity Ligation Assaymentioning

confidence: 99%

Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice

Wang

Chen

et al. 2020

PLoS Genet

Self Cite

View full text Add to dashboard Cite

Approximately 2-15% of couples experience infertility, and around half of these cases are attributed to male infertility. We previously identified TBC1D21 as a sterility-related RabGAP gene derived from infertile men. However, the in vivo function of TBC1D21 in male fertility remains unclear. Here, we show that loss of Tbc1d21 in mice resulted in male infertility, characterized by defects in sperm tail structure and diminished sperm motility. The mitochondria of the sperm-tail had an abnormal irregular arrangement, abnormal diameter, and structural defects. Moreover, the axoneme structure of sperm tails was severely disturbed. Several TBC1D21 interactors were selected via proteomic analysis and functional grouping. Two of the candidate interactors, a subunit protein of translocase in the outer membrane of mitochondria (TOMM20) and an inner arm component of the sperm tail axoneme (Dynein Heavy chain 7, DNAH7), confirmed in vivo physical co-localization with TBC1D21. In addition, TOMM20 and DNAH7 detached and dispersed outside the axoneme in Tbc1d21-deficient sperm, instead of aligning with the axoneme. From a clinical perspective, the transcript levels of TBC1D21 in sperm from teratozoospermia cases were significantly reduced when compared with those in normozoospermia. We concluded that TBC1D21 is critical for mitochondrial and axoneme development of mammalian sperm.

show abstract

“…The assembly of fewer and shorter cilia was also observed in multiciliated cells of Xenopus embryonic epidermis with depleted Katnal2 [7]. In mice, Katnal2 is important at multiple stages of spermatogenesis [9].…”

Section: Introductionmentioning

confidence: 86%

“…However, in Tetrahymena cells lacking Kat2-an ortholog of Katnal2-hyperacetylated microtubules were not observed and the phenotype of the knockout cells was not detectably altered [4]. Interestingly, when co-expressed in HEK293T cells, Katnal2 co-immunoprecipitates with δ-tubulin and ε-tubulin and co-localizes with these non-microtubular tubulins in murine spermatids [9].…”

Section: Introductionmentioning

confidence: 96%

The LisH Domain-Containing N-Terminal Fragment is Important for the Localization, Dimerization, and Stability of Katnal2 in Tetrahymena

Joachimiak

Wacławek

Niziolek

et al. 2020

Cells

View full text Add to dashboard Cite

Katanin-like 2 protein (Katnal2) orthologs have a tripartite domain organization. Two highly conserved regions, an N-terminal LisH (Lis-homology) domain and a C-terminal AAA catalytic domain, are separated by a less conserved linker. The AAA domain of Katnal2 shares the highest amino acid sequence homology with the AAA domain of the canonical katanin p60. Katnal2 orthologs are present in a wide range of eukaryotes, from protists to humans. In the ciliate Tetrahymena thermophila, a Katnal2 ortholog, Kat2, co-localizes with the microtubular structures, including basal bodies and ciliary outer doublets, and this co-localization is sensitive to levels of microtubule glutamylation. The functional analysis of Kat2 domains suggests that an N-terminal fragment containing a LisH domain plays a role in the subcellular localization, dimerization, and stability of Kat2.

show abstract

Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse

Cited by 56 publications

References 59 publications

Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice

Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice

Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice

The LisH Domain-Containing N-Terminal Fragment is Important for the Localization, Dimerization, and Stability of Katnal2 in Tetrahymena

Contact Info

Product

Resources

About