S1P(1) receptor phosphorylation, internalization, and interaction with Rab proteins: effects of sphingosine 1-phosphate, FTY720-P, phorbol esters, and paroxetine
Por:
Carlos Martinez-Morales, Juan, Teresa Romero-Avila, M., Reyes-Cruz, Guadalupe, Adolfo Garcia-Sainz, J.
Publicada:
21 dic 2018
Resumen:
Sphingosine 1-phosphate (S1P) and FTY720-phosphate (FTYp) increased
intracellular calcium in cells expressing S1P1 mCherry-tagged receptors;
the synthetic agonist was considerably less potent. Activation of
protein kinase C by phorbol myristate acetate (PMA) blocked these
effects. The three agents induced receptor phosphorylation and
internalization, with the action of FTYp being more intense. S1P1
receptor-Rab protein (GFP-tagged) interaction was studied using FRET.
The three agents were able to induce S1P1 receptor-Rab5 interaction,
although with different time courses. S1P1 receptor-Rab9 interaction was
mainly increased by the phorbol ester, whereas S1P1 receptor-Rab7
interaction was only increased by FTYp and after a 30-min incubation.
These actions were not observed using dominant negative (GDP-bound) Rab
protein mutants. The data suggested that the three agents induce
interaction with early endosomes, but that the natural agonist induced
rapid receptor recycling, whereas activation of protein kinase C favored
interaction with late endosome and slow recycling and FTYp triggered
receptor interaction with vesicles associated with proteasomal/
lysosomal degradation. The ability of bisindolylmaleimide I and
paroxetine to block some of these actions suggested the activation of
protein kinase C was associated mainly with the action of PMA, whereas G
protein-coupled receptor kinase (GRK) 2 (GRK2) was involved in the
action of the three agents.
Filiaciones:
Carlos Martinez-Morales, Juan:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Ciudad Univ,Ap Postal 70-248, Mexico City 04510, DF, Mexico
Teresa Romero-Avila, M.:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Ciudad Univ,Ap Postal 70-248, Mexico City 04510, DF, Mexico
Reyes-Cruz, Guadalupe:
Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biol Celular, CINVESTAV, Ave Inst Politecn Nacl 2508, Mexico City, DF, Mexico
Adolfo Garcia-Sainz, J.:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Ciudad Univ,Ap Postal 70-248, Mexico City 04510, DF, Mexico
|