Adenylate Kinases 1 and 2 Are Part of the Accessory Structures in the Mouse Sperm Flagellum
ABSTRACT Proper sperm function depends on adequate ATP levels. In the mammalian flagellum, ATP is generated in the midpiece by oxidative respiration and in the principal piece by glycolysis. In locations where ATP is rapidly utilized or produced, adenylate kinases (AKs) maintain a constant adenylate energy charge by interconverting stoichiometric amounts of ATP and AMP with two ADP molecules. We previously identified adenylate kinase 1 and 2 (AK1 and AK2) by mass spectrometry as part of a mouse SDS-insoluble flagellar preparation containing the accessory structures (fibrous sheath, outer dense fibers, and mitochondrial sheath). A germ cell-specific cDNA encoding AK1 was characterized and found to contain a truncated 3' UTR and a different 5' UTR compared to the somatic Ak1 mRNA; however, it encoded an identical protein. Ak1 mRNA was upregulated during late spermiogenesis, a time when the flagellum is being assembled. AK1 was first seen in condensing spermatids and was associated with the outer microtubular doublets and outer dense fibers of sperm. This localization would allow the interconversion of ATP and ADP between the fibrous sheath where ATP is produced by glycolysis and the axonemal dynein ATPases where ATP is consumed. Ak2 mRNA was expressed at relatively low levels throughout spermatogenesis, and the protein was localized to the mitochondrial sheath in the sperm midpiece. AK1 and AK2 in the flagellar accessory structures provide a mechanism to buffer the adenylate energy charge for sperm motility.
- SourceAvailable from: Petras Dzeja
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- "Recently, it was demonstrated that AK1 translocates to the nucleus during cell division and associates with the mitotic spindle to provide energy for chromosome disjunction (Fig. 6.2) (Dzeja et al. 2011a). The discovery of nuclear translocation of AK1 in metaphase is in line with the adenylate kinase role in energy support of motility of cilia and flagella which have 9 + 2 microtubular structures similar to those of mitotic spindle (Cao et al. 2006; Wirschell et al. 2004). In mitotic spindles, AK1 is expected to associate with motor or anchoring proteins as it does with the Oda5 protein of the dynein complex in flagella to provide " on-site " ATP fueling capacity (van Horssen et al. 2009; Wirschell et al. 2004). "
ABSTRACT: The adenylate kinase isoform network is integral to the cellular energetic system and a major player in AMP metabolic signaling circuits. Critical in energy state monitoring and stress response, the dynamic behavior of the adenylate kinase network in governing intracellular, nuclear, and extracellular nucleotide signaling processes has been increasingly revealed. New adenylate kinase mutations have been identified that cause severe human disease phenotypes such as reticular dysgenesis associated with immunodeficiency and sensorineural hearing loss and primary ciliary dyskinesia characteristic of chronic obstructive pulmonary disease. The adenylate kinase family comprises nine major isoforms (AK1–AK9), and several subforms with distinct intracellular localization and kinetic properties designed to support specific cellular processes ranging from muscle contraction, electrical activity, cell motility, unfolded protein response, and mitochondrial/nuclear energetics. Adenylate kinase and AMP signaling is necessary for energetic communication between mitochondria, myofibrils, and the cell nucleus and for metabolic programming facilitating stem cell cardiac differentiation and mitochondrial network formation. Moreover, it was discovered that during cell cycle, the AK1 isoform translocates to the nucleus and associates with the mitotic spindle to provide energy for cell division. Furthermore, deletion of Ak2 gene is embryonically lethal, indicating critical significance of catalyzed phosphotransfer in the crowded mitochondrial intracristae and subcellular spaces for ATP export and intracellular distribution. Taken together, new evidence highlights the importance of the system-wide adenylate kinase isoform network and adenylate kinase-mediated phosphotransfer and AMP signaling in cellular energetics, metabolic sensing, and regulation of nuclear and cell cycle processes which are critical in tissue homeostasis, renewal, and regeneration.Systems Biology of Metabolic and Signaling Networks. Energy, Mass and Information Transfer, Springer Series in Biophysics, Volume 16, Part II edited by Miguel A. Aon, Valdur Saks, Uwe Schlattner, 01/2014: chapter 6: pages 145-162; Springer., ISBN: 978-3-642-38504-9
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- "Adenylate kinase 1 SN Plt * * 27 0.09% [Cao et al. 2006] ATP synthase subunit g, mitochondrial) Plt 11 0.79% [Khan et al. 2009] Mitochondrial pyruvate carrier 1-like "
ABSTRACT: The laboratory evaluation of male infertility remains an essential area of research as 40-60% of infertility cases are attributable to male-related factors. Current sperm analysis methods add only partial information on sperm quality and fertility outcomes. The specific underlying cause of infertility in most cases is unknown, while a proportion of male infertility could be caused by molecular factors such as the absence or abnormal expression of some essential sperm proteins. The objective of this study was to screen for associations between sperm protein profiles and sperm concentration, motility, and DNA fragmentation index in patients undergoing fertility evaluation in a clinical setting. Based on those parameters, semen samples were categorized as either normal or abnormal. We screened 34 semen samples with various abnormal parameters and compared them to 24 normal control samples by using one dimensional (1-D) gel electrophoresis and mass-spectrometry. In this study, we anticipated to establish a normal sperm parameter profile which would be compared to abnormal sperm samples and reveal candidate proteins. Our preliminary results indicate that no normal uniform profile could be established, which affirms the complexity of male fertility and confirms the limitations of standard semen analysis. Four main protein groups were identified in correlation with abnormal DNA fragmentation and/or motility. The first group included sperm nuclear proteins such as the SPANX (sperm protein associated with the nucleus on the X chromosome) isoforms and several types of histones. The second group contained mitochondria-related functions and oxidative stress proteins including Mitochondrial Ferritin, Mitochondrial Single-Stranded DNA Binding Protein, and several isoforms of Peroxiredoxins. Two other protein groups were related to sperm motility such as microtubule-based flagellum and spindle microtubule as well as proteins related to the ubiquitin-proteasome pathway. Further research is required in order to characterize these potential biomarkers of male fertility potential.Systems biology in reproductive medicine 06/2013; 59(3):153-63. DOI:10.3109/19396368.2013.775396 · 1.70 Impact Factor
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ABSTRACT: Flagellar-mediated motility is an indispensable function for cell types as evolutionarily distant as mammalian sperm and kinetoplastid parasites, a large group of flagellated protozoa that includes several important human pathogens. Despite the obvious importance of flagellar motility, little is known about the signalling processes that direct the frequency and wave shape of the flagellar beat, or those that provide the motile cell with the necessary environmental cues that enable it to aim its movement. Similarly, the energetics of the flagellar beat and the problem of a sufficient ATP supply along the entire length of the beating flagellum remain to be explored. Recent proteome projects studying the flagella of mammalian sperm and kinetoplastid parasites have provided important information and have indicated a surprising degree of similarities between the flagella of these two cell types.Trends in Parasitology 03/2007; 23(2):71-7. DOI:10.1016/j.pt.2006.12.002 · 6.22 Impact Factor