ArticleProceedings of the National Academy of Sciences of the United States of America2013
Globin-coupled heme containing oxygen sensor soluble adenylate cyclase in Leishmania prevents cell death during hypoxia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Protist oxygen-sensing and the role of prolyl hydroxylase-regulation of E3(SCF) ubiquitin ligases.Biochimica et biophysica acta. General subjects · 2026Review
- Oxygen and immunity toInfection and immunity · 2025Review
- Evolutionary analysis of the Leishmania major orthologues for the newly identified cyclic AMP response proteins.Archives of microbiology · 2025Article
- Gasocrine hypothesis - a potential supplement to cell theory.Acta biochimica Polonica · 2025Article
- Gas-sensing riboceptors.RNA biology · 2024Article
- Hemoglobin uptake and utilization by human protozoan parasites: a review.Frontiers in cellular and infection microbiology · 2023Review
- Evolutionary analysis of globin domains from kinetoplastids.Archives of microbiology · 2022Article
- Editorial: Signaling in stress sensing and resistance in parasitic protozoa.Frontiers in cellular and infection microbiology · 2022Article
- Nutrient sensing in Leishmania: Flagellum and cytosol.Molecular microbiology · 2021Review
- Large-Scale Phylogenetic Analysis of Trypanosomatid Adenylate Cyclases Reveals Associations with Extracellular Lifestyle and Host-Pathogen Interplay.Genome biology and evolution · 2020Article
- π-Helix controls activity of oxygen-sensing diguanylate cyclases.Bioscience reports · 2020Article
- Evaluation of Modulators of cAMP-Response in Terms of Their Impact on Cell Cycle and Mitochondrial Activity ofFrontiers in pharmacology · 2020Article
- Comparative genomics of Leishmania (Mundinia).BMC genomics · 2019Article
- Druggable Targets in Cyclic Nucleotide Signaling Pathways in Apicomplexan Parasites and Kinetoplastids against Disabling Protozoan Diseases in Humans.International journal of molecular sciences · 2019Review
- Adenylate Cyclases ofPathogens (Basel, Switzerland) · 2018Review
- Hypoxia, Hypoxia-Inducible Factor-1α, and Innate Antileishmanial Immune Responses.Frontiers in immunology · 2018Review
- Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mechanism and Role of Globin-Coupled Sensor Signalling.Advances in microbial physiology · 2017Review
- Reactivation of flagellar motility in demembranated Leishmania reveals role of cAMP in flagellar wave reversal to ciliary waveform.Scientific reports · 2016Article
- An O2-sensing stressosome from a Gram-negative bacterium.Nature communications · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Globin and adenylate cyclase play individually numerous crucial roles in eukaryotic organisms. Comparison of the amino acid sequences of globins and adenylate cyclase from prokaryotic to eukaryotic organisms suggests that they share an early common ancestor, even though these proteins execute different functions in these two kingdoms. The latest studies of biological signaling molecules in both prokaryotic and eukaryotic organisms have discovered a new class of heme-containing proteins that act as sensors. The protein of the globin family is still unknown in the trypanosomatid parasites, Trypanosome and Leishmania. In addition, globin-coupled heme containing adenylate cyclase is undescribed in the literature. Here we report a globin-coupled heme containing adenylate cyclase (HemAC-Lm) in the unicellular eukaryotic organism Leishmania. The protein exhibits spectral properties similar to neuroglobin and cytoglobin. Localization studies and activity measurements demonstrate that the protein is present in cytosol and oxygen directly stimulates adenylate cyclase activity in vivo and in vitro. Gene knockdown and overexpression studies suggest that O2-dependent cAMP signaling via protein kinase A plays a fundamental role in cell survival through suppression of oxidative stress under hypoxia. In addition, the enzyme-dependent cAMP generation shows a stimulatory as well as inhibitory role in cell proliferation of Leishmania promastigotes during normoxia. Our work begins to clarify how O2-dependent cAMP generation by adenylate cyclase is likely to function in cellular adaptability under various O2 tensions.
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