Musikant Daniel, Ferri Gabriel, Durante Ignacio M, Buscaglia Carlos A, Altschuler Daniel L, Edreira Martin M
IQUIBICEN-CONICET-Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
Mol Biochem Parasitol. 2017 Jan;211:67-70. doi: 10.1016/j.molbiopara.2016.10.003. Epub 2016 Oct 27.
Mechanistic details of the modulation by cAMP of Trypanosoma cruzi host cell invasion remain ill-defined. Here we report that activation of host's Epac1 stimulated invasion, whereas specific pharmacological inhibition or maneuvers that alter Epac1 subcellular localization significantly reduced invasion. Furthermore, while specific activation of host cell PKA showed no effect, its inhibition resulted in an increased invasion, revealing a crosstalk between the PKA and Epac signaling pathways during the process of invasion. Therefore, our data suggests that subcellular localization of Epac might be playing an important role during invasion and that specific activation of the host cell cAMP/Epac1 pathway is required for cAMP-mediated invasion.
环磷酸腺苷（cAMP）对克氏锥虫宿主细胞入侵的调节机制细节仍不清楚。在此我们报告，宿主的交换蛋白直接激活环磷腺苷酸结合蛋白1（Epac1）的激活会刺激入侵，而特异性药理抑制或改变Epac1亚细胞定位的操作会显著降低入侵。此外，虽然宿主细胞蛋白激酶A（PKA）的特异性激活没有效果，但其抑制会导致入侵增加，这揭示了入侵过程中PKA和Epac信号通路之间的相互作用。因此，我们的数据表明，Epac的亚细胞定位可能在入侵过程中起重要作用，并且cAMP介导的入侵需要宿主细胞cAMP/Epac1信号通路的特异性激活。
