Role of Adenylate Kinase Type 7 Expression on Cilia Motility: Possible Link in Primary Ciliary Dyskinesia

Milara, Javier; Armengot, M; Mata, Manuel; Morcillo, Esteban J.; Cortijo, Julio

doi:10.2500/ajra.2010.24.3468

Cited by 23 publications

(28 citation statements)

References 17 publications

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“…A sperm-specific phenotype with incomplete mitochondrial sheath, dysplasia of the fibrous sheath and lack of central pair microtubules with axonemal disorganization was also reported for AK7 [70]. PCD-associated mutations and decreased AK7 expression have also been reported in PCD patients [76,80]. Tissue specific effects of AK7 mutations are likely, since a missense mutation was reported to affect the expression in the testis, but not in multiciliated tissues [70].…”

Section: Genetic Mutations Causing Sperm Tail-specific Phenotypesmentioning

confidence: 86%

Sperm defects in primary ciliary dyskinesia and related causes of male infertility

Sironen

Shoemark

Patel

et al. 2019

Cell. Mol. Life Sci.

179

159

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The core axoneme structure of both the motile cilium and sperm tail has the same ultrastructural 9 + 2 microtubular arrangement. Thus, it can be expected that genetic defects in motile cilia also have an effect on sperm tail formation. However, recent studies in human patients, animal models and model organisms have indicated that there are differences in components of specific structures within the cilia and sperm tail axonemes. Primary ciliary dyskinesia (PCD) is a genetic disease with symptoms caused by malfunction of motile cilia such as chronic nasal discharge, ear, nose and chest infections and pulmonary disease (bronchiectasis). Half of the patients also have situs inversus and in many cases male infertility has been reported. PCD genes have a role in motile cilia biogenesis, structure and function. To date mutations in over 40 genes have been identified cause PCD, but the exact effect of these mutations on spermatogenesis is poorly understood. Furthermore, mutations in several additional axonemal genes have recently been identified to cause a sperm-specific phenotype, termed multiple morphological abnormalities of the sperm flagella (MMAF). In this review, we discuss the association of PCD genes and other axonemal genes with male infertility, drawing particular attention to possible differences between their functions in motile cilia and sperm tails.

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Section: Genetic Mutations Causing Sperm Tail-specific Phenotypesmentioning

confidence: 86%

Sperm defects in primary ciliary dyskinesia and related causes of male infertility

Sironen

Shoemark

Patel

et al. 2019

Cell. Mol. Life Sci.

179

159

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“…Genes involved in PCD have been characterized, but not all cases can be described genetically [4]. PCD seems to be linked with malfunctioning in adenosine triphosphate metabolism [9,10]. In TEM analysis different defects are seen in PCD, but only some larger series describing these defects exist [11-18].…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural pathology of primary ciliary dyskinesia: report about 125 cases in Germany

Theegarten

Ebsen

2011

Diagn Pathol

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BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetically induced disorder of cilia inducing mainly respiratory diseases. Transmission electron microscopy (TEM) analysis of ciliary ultrastructure is classically used for diagnosis. We report our experience of TEM investigations in a large series of patients.MethodsTEM analysis performed of 742 biopsies from patients with suspected PCD was reviewed retrospectively. Ultrastructural defects were analysized further in 125 cases with changes typical for PCD.ResultsIn 18.1% of patients diagnosis of PCD was made because of morphological alterations, in 68.2% secondary changes were seen. In 13.7% material was not feasible for analysis. Mostly defects of dynein arms were detected in PCD (96.8%). In particular defects of the inner arms (51.2%) and combined dynein defects (37.6%) were found. Total loss of dynein arms was dominant. Only in 3.2% deficiencies of central structures were found alone. Associated situs inversus or dextracardia was reported clinically in 21.4%.ConclusionsTEM analysis is possible in most patients and a useful tool for diagnosis of PCD. Functional and genetic analysis should be done additionally. Registers should be installed to collect all available informations and push further research.

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“…Several other AK enzymes have not been fully characterized in mouse sperm but may also have important functions. For example, AK7 has an essential role and causes primary cilia dyskinesia when mutated [13,[42][43][44]. In the mouse, the Ak7 gene was serendipitously mutated by a frame-shift mutation with the result that the male mice are infertile due to the absence of the axonemal central microtubule pair and abnormal spermatogenesis; the few sperm that are recoverable are immotile.…”

Section: Adenine Nucleotide Metabolism Regulates Sperm Motilitymentioning

confidence: 98%

Adenine Nucleotide Metabolism and a Role for AMP in Modulating Flagellar Waveforms in Mouse Sperm1

Vadnais¹,

Cao²,

Aghajanian³

et al. 2014

Biology of Reproduction

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While most ATP, the main energy source driving sperm motility, is derived from glycolysis and oxidative phosphorylation, the metabolic demands of the cell require the efficient use of power stored in high-energy phosphate bonds. In times of high energy consumption, adenylate kinase (AK) scavenges one ATP molecule by transphosphorylation of two molecules of ADP, simultaneously yielding one molecule of AMP as a by-product. Either ATP or ADP supported motility of detergent-modeled cauda epididymal mouse sperm, indicating that flagellar AKs are functional. However, the ensuing flagellar waveforms fueled by ATP or ADP were qualitatively different. Motility driven by ATP was rapid but restricted to the distal region of the sperm tail, whereas ADP produced slower and more fluid waves that propagated down the full flagellum. Characterization of wave patterns by tracing and superimposing the images of the flagella, quantifying the differences using digital image analysis, and computer-assisted sperm analysis revealed differences in the amplitude, periodicity, and propagation of the waves between detergent-modeled sperm treated with either ATP or ADP. Surprisingly, addition of AMP to the incubation medium containing ATP recapitulated the pattern of sperm motility seen with ADP alone. In addition to AK1 and AK2, which we previously demonstrated are present in outer dense fibers and mitochondrial sheath of the mouse sperm tail, we show that another AK, AK8, is present in a third flagellar compartment, the axoneme. These results extend the known regulators of sperm motility to include AMP, which may be operating through an AMP-activated protein kinase.

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Role of Adenylate Kinase Type 7 Expression on Cilia Motility: Possible Link in Primary Ciliary Dyskinesia

Abstract: AK7 expression was correlated with CBF in vitro and in nasal biopsy specimens from patients with PCD, which may have contributed to the ciliary malfunction observed in our patients with PCD.

Cited by 23 publications

References 17 publications

Sperm defects in primary ciliary dyskinesia and related causes of male infertility

Sperm defects in primary ciliary dyskinesia and related causes of male infertility

Ultrastructural pathology of primary ciliary dyskinesia: report about 125 cases in Germany

Adenine Nucleotide Metabolism and a Role for AMP in Modulating Flagellar Waveforms in Mouse Sperm1

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