Oligomerization of equilibrative nucleoside transporters: a novel regulatory and functional mechanism involving PKC and PP1.
Por:
Grañe-Boladeras N, Williams D, Tarmakova Z, Stevanovic K, Villani LA, Mehrabi P, Siu KWM, Pastor-Anglada M and Coe IR
Publicada:
1 mar 2019
Ahead of Print:
6 dic 2018
Resumen:
Equilibrative nucleoside transporters (ENTs) translocate nucleosides and nucleobases across plasma membranes, as well as a variety of anti-cancer, -viral, and -parasite nucleoside analogs. They are also key members of the purinome complex and regulate the protective and anti-inflammatory effects of adenosine. Despite their important role, little is known about the mechanisms involved in their regulation. We conducted membrane yeast 2-hybrid and coimmunoprecipitation studies and identified, for the first time to our knowledge, the existence of protein-protein interactions between human ENT1 and ENT2 (hENT1 and hENT2) proteins in human cells and the formation of hetero- and homo-oligomers at the plasma membrane and the submembrane region. The use of NanoLuc Binary Technology allowed us to analyze changes in the oligomeric status of hENT1 and hENT2 and how they rapidly modify the uptake profile for nucleosides and nucleobases and allow cells to respond promptly to external signals or changes in the extracellular environment. These changes in hENTs oligomerization are triggered by PKC activation and subsequent action of protein phosphatase 1.-Grañe-Boladeras, N., Williams, D., Tarmakova, Z., Stevanovic, K., Villani, L. A., Mehrabi, P., Siu, K. W. M., Pastor-Anglada, M., Coe, I. R. Oligomerization of equilibrative nucleoside transporters: a novel regulatory and functional mechanism involving PKC and PP1.
Filiaciones:
Grañe-Boladeras N:
Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada
Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine, University of Barcelona, Barcelona, Spain
National Biomedical Research Institute of Liver and Gastrointestinal Diseases, Barcelona, Spain
Williams D:
Department of Chemistry, York University, Toronto, Ontario, Canada
and
Tarmakova Z:
Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada
Stevanovic K:
Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada
Villani LA:
Department of Biology, York University, Toronto, Ontario, Canada
Mehrabi P:
Department of Biology, York University, Toronto, Ontario, Canada
Siu KWM:
Department of Chemistry, York University, Toronto, Ontario, Canada
and
Pastor-Anglada M:
Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine, University of Barcelona, Barcelona, Spain
National Biomedical Research Institute of Liver and Gastrointestinal Diseases, Barcelona, Spain
Coe IR:
Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada
Open Access
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