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

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

Buenos Aires

Jornada; 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;1 and can be regulated by pH. It was demostrated that coexpression of FaPIP1;1 with FaPIP2;1 in Xenopus oocytes affects gating sensitivity in terms of cytosolic acidification, showing that interactions between different subunits modify the cooperativity among monomers. In our previous work we have seen that FaPIP2;1 responds just like a mechanosensitive aquaporin and we propose that FaPIP2;1-FaPIP1;1 heterotetramers would be a suitable model to study the cooperativity in mechanical regulation of aquaporins. In the current work we performed simulations in order to study the osmotic response of Xenopus oocytes expressing FaPIP2;1 homotetramers and FaPIP2;1-FaPIP1;1 heterotetramers. The model is based on the relationship between the initial permeability and the oocyte pressure-volume curve. These variables are related by a nonlinear function that was experimentally determined in a previous work. Volume changes were registered 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 results show that Pf decreases as the oocyte volume increases, the same fenomena that was observed in different mechanosensitive plant and animal aquaporins. In addition, Pf decreases faster in oocytes with FaPIP2;1 homotetramers than in oocytes with FaPIP2;1-FaPIP1;1 heterotetramers. This suggests that the interaction between different monomers affect the mechanosensitivity of aquaporins evidencing a cooperative effect.