Lateral membrane organization of PI(4,5)P2

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The modern understanding of biological membranes acknowledges the presence of a highly heterogeneous distribution of lipid components.  This heterogeneity is responsible for the formation of a lateral organization of membrane components which is known to play critical roles in multiple biological processes. The impact of lateral organization on the activity of bioactive lipids is particularly interesting.

 

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) stands out from other plasma membrane lipids as one of the most important regulators of membrane-associated signaling events. PI(4,5)P2 is able to engage in a multitude of simultaneous cellular functions that are temporally and spatially regulated through the presence of localized transient pools of PI(4,5)P2 in the membrane. These pools are crucial for the recruitment, activation, and organization of signaling proteins and consequent regulation of downstream signaling.

Fig.1: Membrane processes associated with or dependent on PI(4,5)P2. L. Borges-Araújo and F. Fernandes..Molecules 2020, 25(17), 3885; https://doi.org/10.3390/molecules25173885

In our lab we are working on the characterization of the lateral organization of the key phospholipid PI(4,5)P2, and on the mechanisms responsible for its regulation. Using biophysical methodologies we follow a bottom-up approach to solve this problems in both model and cellular membranes.

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Fig.2: Giant Unilamellar Vesicles loaded with fluorescent analogues of PI(4,5)P2 and imaged with confocal microscopy. Sarmento et al. 2014. Biochmica et Biophysica Acta-Biomembranes 1838: 822. https://doi.org/10.1016/j.bbamem.2013.11.020

Fig3: Confocal Microscopy of HEK293 cells expressing a PI(4,5)P2-binding Pleckstrin Homology domains tagged with a fluorescent protein.

The impact of divalent cations such as calcium on PI(4,5)P2 organization is particularly interesting given its potential to influence calcium signalling and the availability of PI(4,5)P2.

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Fig.4: Calcium-induced clustering of PI(4,5)P2. For details see L. Borges-Araújo and F. Fernandes..Molecules 2020, 25(17), 3885; https://doi.org/10.3390/molecules25173885