Aquaporin mechanical regulation: a simulation approach with FaPIP homo and heterotetramers

FLORENCIA GUASTAFERRI; AGUSTÍN CAVIGLIA; OLIVER GIBSON; RAMIRO GOLDMAN; MOIRA SUTKA; LUCIANO GALIZIA; MARCELO OZU

Buenos Aires

Congreso; Primeras Jornadas Virtuales de la Sociedad Argentina de Biofísica; 2020

Sociedad Argentina de Biofísica

FaPIP2;1 is a high-Pf strawberry water channel that forms heterotetramers with FaPIP1;1and can be regulated by pH. It was demostrated that coexpression of FaPIP1;1 withFaPIP2;1 in Xenopus oocytes affects gating sensitivity in terms of cytosolic acidification,showing that interactions between different subunits modify the cooperativity amongmonomers. In our previous work we have seen that FaPIP2;1 responds just like amechanosensitive aquaporin and we propose that FaPIP2;1-FaPIP1;1 heterotetramerswould be a suitable model to study the cooperativity in mechanical regulation ofaquaporins. In the current work we performed simulations in order to study the osmoticresponse of Xenopus oocytes expressing FaPIP2;1 homotetramers and FaPIP2;1-FaPIP1;1heterotetramers. The model is based on the relationship between the initial permeabilityand the oocyte pressure-volume curve. These variables are related by a nonlinearfunction that was experimentally determined in a previous work. Volume changes wereregistered during oocyte swelling induced by a hypo-osmotic shock of 160 mOsm·kg−1.The model can reproduce the osmotic response and predict the water permeability (Pf)dynamics of oocytes expressing either FaPIP2;1 or FaPIP2;1-FaPIP1;1. Simulation resultsshow that Pf decreases as the oocyte volume increases, the same fenomena that wasobserved in different mechanosensitive plant and animal aquaporins. In addition, Pfdecreases faster in oocytes with FaPIP2;1 homotetramers than in oocytes with FaPIP2;1-FaPIP1;1 heterotetramers. This suggests that the interaction between differentmonomers affect the mechanosensitivity of aquaporins evidencing a cooperative effect.