scholarly journals Wampa is a dynein subunit required for axonemal assembly and male fertility in Drosophila

2019 ◽  
Author(s):  
Elisabeth Bauerly ◽  
Kexi Yi ◽  
Matthew C. Gibson
Keyword(s):  
Male Fertility ◽  
Primary Ciliary Dyskinesia ◽  
Functional Role ◽  
Essential Role ◽  
Respiratory Infections ◽  
Pathological Features ◽  
Dynein Arms ◽  
Cilia And Flagella ◽  
Ciliary Dyskinesia

AbstractAxonemal dyneins are motor proteins that form the inner and outer arms of the axoneme in cilia and flagella. Defects in dynein arms are the leading cause of primary ciliary dyskinesia (PCD), which is characterized by chronic respiratory infections, situs inversus, and sterility. Despite current understanding of pathological features associated with PCD, many of their causative genes still remain elusive. Here we analyze genetic requirements for wampa (wam), a previously uncharacterized component of the outer dynein arm that is essential for male fertility. In addition to a role in outer dynein arm formation, we uncovered additional requirements during spermatogenesis, including regulation of remodeling events for the mitochondria and the nucleus. Due to the conserved nature of axonemal dyneins and their essential role in both PCD and fertility, this study advances our understanding of the pathology of PCD, as well as the functional role of dyneins in axonemal formation and spermatogenesis.

scholarly journals Essential role of CFAP53 in sperm flagellum biogenesis

2021 ◽  
Author(s):  
Bingbing Wu ◽  
Xiaochen Yu ◽  
Chao Liu ◽  
Lina Wang ◽  
Tao Huang ◽  
...  
Keyword(s):  
Male Fertility ◽  
Essential Role ◽  
Expression Level ◽  
Research Progress ◽  
Male Mice ◽  
Sperm Tail ◽  
Sperm Flagellum ◽  
Associated Proteins ◽  
Cilia And Flagella

AbstractThe sperm flagellum is essential for male fertility. Despite vigorous research progress towards understanding the pathogenesis of flagellum-related diseases, much remains unknown about the mechanisms underlying the flagellum biogenesis itself. Here, we show that the cilia and flagella associated protein 53 (Cfap53) gene is predominantly expressed in testes, and it is essential for sperm flagellum biogenesis. The knockout of this gene resulted in complete infertility in male mice but not in the females. CFAP53 localized to the manchette and sperm tail during spermiogenesis, the knockout of this gene impaired flagellum biogenesis. Furthermore, we identified two manchette and sperm tail-associated proteins that interacted with CFAP53 during spermiogenesis. The disruption of Cfap53 decreased the expression level of these two proteins and disrupted their localization in spermatids. Together, our results suggest that CFAP53 is an essential protein for sperm flagellum biogenesis, and its mutations might be associated with MMAF.

scholarly journals Essential Role of CFAP53 in Sperm Flagellum Biogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Bingbing Wu ◽  
Xiaochen Yu ◽  
Chao Liu ◽  
Lina Wang ◽  
Tao Huang ◽  
...  
Keyword(s):  
Male Fertility ◽  
Essential Role ◽  
Research Progress ◽  
Male Mice ◽  
Sperm Tail ◽  
Morphological Abnormalities ◽  
Sperm Flagellum ◽  
Associated Proteins ◽  
Cilia And Flagella

The sperm flagellum is essential for male fertility. Despite vigorous research progress toward understanding the pathogenesis of flagellum-related diseases, much remains unknown about the mechanisms underlying the flagellum biogenesis itself. Here, we show that the cilia and flagella associated protein 53 (Cfap53) gene is predominantly expressed in testes, and it is essential for sperm flagellum biogenesis. The knockout of this gene resulted in complete infertility in male mice but not in the females. CFAP53 localized to the manchette and sperm tail during spermiogenesis, the knockout of this gene impaired flagellum biogenesis. Furthermore, we identified two manchette and sperm tail-associated proteins that interacted with CFAP53 during spermiogenesis. Together, our results suggest that CFAP53 is an essential protein for sperm flagellum biogenesis, and its mutations might be associated with multiple morphological abnormalities of the flagella (MMAF).

scholarly journals CFAP61 is required for sperm flagellum formation and male fertility in human and mouse

2021 ◽  
Author(s):  
Siyu Liu ◽  
Jintao Zhang ◽  
Zine Eddine Kherraf ◽  
Shuya Sun ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Male Fertility ◽  
Primary Ciliary Dyskinesia ◽  
Exon Skipping ◽  
Intraflagellar Transport ◽  
Transport Proteins ◽  
Radial Spoke ◽  
Sperm Flagellum ◽  
Cilia And Flagella ◽  
Ciliary Dyskinesia ◽  
Human And Mouse

Defects in the structure or motility of cilia and flagella may lead to severe diseases such as primary ciliary dyskinesia (PCD), a multisystemic disorder with heterogeneous manifestations affecting primarily respiratory and reproductive functions. We report that CFAP61 is a conserved component of the Calmodulin and radial Spoke associated Complex (CSC) of cilia. We find that a CFAP61 splice variant, c.143+5G>A, causes exon skipping in human, inducing a multiple morphological abnormalities of the flagella (MMAF) phenotype. We generated Cfap61 knockout mice that recapitulate the infertility phenotype of the human CFAP61 mutation, but without other symptoms usually observed in PCD. We find that CFAP61 interacts with the CSC, radial spoke stalk and RS head. During early stages of Cfap61-/- spermatid development, the assembly of RS components is impaired. With the progress of spermiogenesis, the axoneme in Cfap61-/- cells becomes unstable and scatters, and the distribution of intraflagellar transport proteins is disrupted.

scholarly journals Diagnostics and Management of Male Infertility in Primary Ciliary Dyskinesia

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1550
Author(s):  
Channa N. Jayasena ◽  
Anu Sironen
Keyword(s):  
Male Fertility ◽  
Primary Ciliary Dyskinesia ◽  
Reproductive Tract ◽  
Respiratory Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Heavy Chains ◽  
Sperm Development ◽  
Motile Cilia ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD), a disease caused by the malfunction of motile cilia, manifests mainly with chronic recurrent respiratory infections. In men, PCD is also often associated with infertility due to immotile sperm. Since causative mutations for PCD were identified in over 50 genes, the role of these genes in sperm development should be investigated in order to understand the effect of PCD mutations on male fertility. Previous studies showed that different dynein arm heavy chains are present in respiratory cilia and sperm flagellum, which may partially explain the variable effects of mutations on airways and fertility. Furthermore, recent studies showed that male reproductive tract motile cilia may play an important part in sperm maturation and transport. In some PCD patients, extremely low sperm counts were reported, which may be due to motile cilia dysfunction in the reproductive tract rather than problems with sperm development. However, the exact roles of PCD genes in male fertility require additional studies, as do the treatment options. In this review, we discuss the diagnostic and treatment options for men with PCD based on the current knowledge.

scholarly journals Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility

Science ◽  
2021 ◽  
Vol 371 (6525) ◽  
pp. eabd4914
Author(s):  
Sudarshan Gadadhar ◽  
Gonzalo Alvarez Viar ◽  
Jan Niklas Hansen ◽  
An Gong ◽  
Aleksandr Kostarev ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Male Fertility ◽  
Electron Tomography ◽  
Structural Basis ◽  
Cellular Functions ◽  
Flagellar Beat ◽  
Cryo Electron Tomography ◽  
Axonemal Dynein ◽  
Dynein Arms ◽  
Cilia And Flagella

Posttranslational modifications of the microtubule cytoskeleton have emerged as key regulators of cellular functions, and their perturbations have been linked to a growing number of human pathologies. Tubulin glycylation modifies microtubules specifically in cilia and flagella, but its functional and mechanistic roles remain unclear. In this study, we generated a mouse model entirely lacking tubulin glycylation. Male mice were subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells. Using cryo–electron tomography, we showed that lack of glycylation caused abnormal conformations of the dynein arms within sperm axonemes, providing the structural basis for the observed dysfunction. Our findings reveal the importance of microtubule glycylation for controlled flagellar beating, directional sperm swimming, and male fertility.

scholarly journals Mutations in C11orf70 Cause Primary Ciliary Dyskinesia with Randomization of Left/Right Body Asymmetry Due to Defects of Outer and Inner Dynein Arms

2018 ◽  
Vol 102 (5) ◽  
pp. 973-984 ◽  
Author(s):  
Inga M. Höben ◽  
Rim Hjeij ◽  
Heike Olbrich ◽  
Gerard W. Dougherty ◽  
Tabea Nöthe-Menchen ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Body Asymmetry ◽  
Dynein Arms ◽  
Ciliary Dyskinesia

scholarly journals Pcdp1 is a central apparatus protein that binds Ca2+-calmodulin and regulates ciliary motility

2010 ◽  
Vol 189 (3) ◽  
pp. 601-612 ◽  
Author(s):  
Christen G. DiPetrillo ◽  
Elizabeth F. Smith
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Calcium Concentration ◽  
Beat Frequency ◽  
Calcium Sensor ◽  
Central Pair ◽  
Ciliary Motility ◽  
Significant Impairment ◽  
Central Apparatus ◽  
Cilia And Flagella ◽  
Ciliary Dyskinesia

For all motile eukaryotic cilia and flagella, beating is regulated by changes in intraciliary calcium concentration. Although the mechanism for calcium regulation is not understood, numerous studies have shown that calmodulin (CaM) is a key axonemal calcium sensor. Using anti-CaM antibodies and Chlamydomonas reinhardtii axonemal extracts, we precipitated a complex that includes four polypeptides and that specifically interacts with CaM in high [Ca2+]. One of the complex members, FAP221, is an orthologue of mammalian Pcdp1 (primary ciliary dyskinesia protein 1). Both FAP221 and mammalian Pcdp1 specifically bind CaM in high [Ca2+]. Reduced expression of Pcdp1 complex members in C. reinhardtii results in failure of the C1d central pair projection to assemble and significant impairment of motility including uncoordinated bends, severely reduced beat frequency, and altered waveforms. These combined results reveal that the central pair Pcdp1 (FAP221) complex is essential for control of ciliary motility.

scholarly journals Mutations in the dynein assembly factor PF22 (DNAAF3) cause primary ciliary dyskinesia with absent dynein arms

Cilia ◽  
2012 ◽  
Vol 1 (S1) ◽  
Author(s):  
M Schmidts ◽  
J Freshour ◽  
NT Loges ◽  
A Dritsoula ◽  
D Antony ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Assembly Factor ◽  
Dynein Arms ◽  
Ciliary Dyskinesia
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