Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates

Kumar, Ujjwal; Saier, Milton H.

doi:10.1111/jeu.12156

Cited by 4 publications

(3 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, results derived from recent bioinformatic analyses suggest that there are more than 10 equilibrative nucleoside transporter genes present in the T . thermophila genome [ 27 , 28 ], indirectly confirming those early observations. However, the functions and locations of these putative transporters, as well as the mode of transport, require further investigation.…”

Section: Resultssupporting

confidence: 80%

Effects of six pyrimidine analogs on the growth of Tetrahymena thermophila and their implications in pyrimidine metabolism

Harpel,

Chang,

Circelli

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Tetrahymena are ciliated protists that have been used to study the effects of toxic chemicals, including anticancer drugs. In this study, we tested the inhibitory effects of six pyrimidine analogs (5-fluorouracil, floxuridine, 5’-deoxy-5-fluorouridine, 5-fluorouridine, gemcitabine, and cytarabine) on wild-type CU428 and conditional mutant NP1 Tetrahymena thermophila at room temperature and the restrictive temperature (37°C) where NP1 does not form the oral apparatus. We found that phagocytosis was not required for pyrimidine analog entry and that all tested pyrimidine analogs inhibited growth except for cytarabine. IC50 values did not significantly differ between CU428 and NP1 for the same analog at either room temperature or 37°C. To investigate the mechanism of inhibition, we used two pyrimidine bases (uracil and thymine) and three nucleosides (uridine, thymidine, and 5-methyluridine) to determine whether the inhibitory effects from the pyrimidine analogs were reversible. We found that the inhibitory effects from 5-fluorouracil could be reversed by uracil and thymine, from floxuridine could be reversed by thymidine, and from 5’-deoxy-5-fluorouridine could be reversed by uracil. None of the tested nucleobases or nucleosides could reverse the inhibitory effects of gemcitabine or 5-fluorouridine. Our results suggest that the five pyrimidine analogs act on different sites to inhibit T. thermophila growth and that nucleobases and nucleosides are metabolized differently in Tetrahymena.

show abstract

Section: Resultssupporting

confidence: 80%

Effects of six pyrimidine analogs on the growth of Tetrahymena thermophila and their implications in pyrimidine metabolism

Harpel,

Chang,

Circelli

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Transporter proteins in this system have the ability to move one or more types of nucleotides across membranes, with functional redundancies [16,26]. Indeed, results derived from recent bioinformatic analyses suggest that there are more than 10 equilibrative nucleoside transporter genes present in the T. thermophila genome [27,28], indirectly confirming those early observations. However, the functions and locations of these putative transporters, as well as the mode of transport, require further investigation.…”

Section: The Uptake Of Pyrimidine Bases and Nucleosides In T Thermoph...supporting

confidence: 58%

Effects of six pyrimidine analogs on the growth ofTetrahymena thermophilaand their implications in pyrimidine metabolism

Chang

Harpel

Circelli

et al. 2023

Preprint

View full text Add to dashboard Cite

Tetrahymenaare ciliated protists that have been used to study the effects of toxic chemicals, including anticancer drugs. In this study, we tested the inhibitory effects of six pyrimidine analogs (5-fluorouracil, floxuridine, 5’-deoxy-5-fluorouridine, 5-fluorouridine, gemcitabine, cytarabine) on wild-type CU428 and conditional mutant NP1Tetrahymena thermophilaat room temperature and the restrictive temperature (37°C) where NP1 does not form the oral apparatus. We found that cytarabine was the only tested analog that did not inhibit growth, and phagocytosis was not required for pyrimidine analog entry. IC50 values did not significantly differ between strains for the same analog at either temperature. To investigate the mechanism of inhibition, we used two pyrimidine bases (uracil and thymine) and three nucleosides (uridine, thymidine, 5-methyluridine) to help determine whether the inhibitory effects from analogs were reversible. We found that the inhibitory effects from 5-fluorouracil could be reversed by uracil and thymine, from floxuridine could be reversed by thymidine, and from 5’-deoxy-5-fluorouridine could be reversed by uracil. None of the tested nucleobases or nucleosides could reverse the inhibitory effects of gemcitabine or 5-fluorouridine. Our results suggest that the five pyrimidine analogs act on different sites to inhibitT. thermophilagrowth and that nucleobases and nucleosides are metabolized differently.

show abstract

“…This can be concluded from the effect of the H + ‐ATPase inhibitor, concanamycin B (Grønlien et al, ), which inhibits [Ca 2+ ] i downregulation after exocytosis stimulation (Plattner et al, ), as outlined in Sections VI and XII. An abundance of primary and secondary active transporters and channels have been implied by bioinformatic analysis of the genomic databases of P. tetraurelia , T. thermophila and of the fish pathogen, Ichthyophthirius multifiliis (Kumar & Saier, ).…”

Section: Downregulation Of the Most Common Activation Mechanismsmentioning

confidence: 99%

Signalling in ciliates: long- and short-range signals and molecular determinants for cellular dynamics

Plattner

2015

Biol Rev

View full text Add to dashboard Cite

In ciliates, unicellular representatives of the bikont branch of evolution, inter- and intracellular signalling pathways have been analysed mainly in Paramecium tetraurelia, Paramecium multimicronucleatum and Tetrahymena thermophila and in part also in Euplotes raikovi. Electrophysiology of ciliary activity in Paramecium spp. is a most successful example. Established signalling mechanisms include plasmalemmal ion channels, recently established intracellular Ca -release channels, as well as signalling by cyclic nucleotides and Ca . Ca -binding proteins (calmodulin, centrin) and Ca -activated enzymes (kinases, phosphatases) are involved. Many organelles are endowed with specific molecules cooperating in signalling for intracellular transport and targeted delivery. Among them are recently specified soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), monomeric GTPases, H -ATPase/pump, actin, etc. Little specification is available for some key signal transducers including mechanosensitive Ca -channels, exocyst complexes and Ca -sensor proteins for vesicle-vesicle/membrane interactions. The existence of heterotrimeric G-proteins and of G-protein-coupled receptors is still under considerable debate. Serine/threonine kinases dominate by far over tyrosine kinases (some predicted by phosphoproteomic analyses). Besides short-range signalling, long-range signalling also exists, e.g. as firmly installed microtubular transport rails within epigenetically determined patterns, thus facilitating targeted vesicle delivery. By envisaging widely different phenomena of signalling and subcellular dynamics, it will be shown (i) that important pathways of signalling and cellular dynamics are established already in ciliates, (ii) that some mechanisms diverge from higher eukaryotes and (iii) that considerable uncertainties still exist about some essential aspects of signalling.

show abstract

Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates

Cited by 4 publications

References 103 publications

Effects of six pyrimidine analogs on the growth of Tetrahymena thermophila and their implications in pyrimidine metabolism

Effects of six pyrimidine analogs on the growth of Tetrahymena thermophila and their implications in pyrimidine metabolism

Effects of six pyrimidine analogs on the growth ofTetrahymena thermophilaand their implications in pyrimidine metabolism

Signalling in ciliates: long- and short-range signals and molecular determinants for cellular dynamics

Contact Info

Product

Resources

About