Membrane Order Is a Key Regulator of Divalent Cation-Induced Clustering of PI(3,5)P2 and PI(4,5)P2

0480168 - ÚFCH JH 2018 RIV US eng J - Journal Article
Sarmento, Maria Joäo - Coutinho, A. - Fedorov, A. - Prieto, M. - Fernandes, F.
Membrane Order Is a Key Regulator of Divalent Cation-Induced Clustering of PI(3,5)P2 and PI(4,5)P2.
Langmuir. Roč. 33, č. 43 (2017), s. 12463-12477. ISSN 0743-7463
Institutional support: RVO:61388955
Keywords : cell membranes * fluorescence spectroscopy * cluster analysis
OECD category: Physical chemistry
Impact factor: 3.789, year: 2017

Although the evidence for the presence of functionally important nanosized phosphorylated phosphoinositide (PIP)-rich domains within cellular membranes has accumulated, very limited information is available regarding the structural determinants for compartmentalization of these phospholipids. Here, we used a combination of fluorescence spectroscopy and microscopy techniques to characterize differences in divalent cation-induced clustering of PI(4,5)P2 and PI(3,5)P2. Through these methodologies we were able to detect differences in divalent cation-induced clustering efficiency and cluster size. Ca2+-induced PI(4,5)P2 clusters are shown to be significantly larger than the ones observed for PI(3,5)P2. Clustering of PI(4,5)P2 is also detected at physiological concentrations of Mg2+, suggesting that in cellular membranes, these molecules are constitutively driven to clustering by the high intracellular concentration of divalent cations. Importantly, it is shown that lipid membrane order is a key factor in the regulation of clustering for both PIP isoforms, with a major impact on cluster sizes. Clustered PI(4,5)P2 and PI(3,5)P2 are observed to present considerably higher affinity for more ordered lipid phases than the monomeric species or than PI(4)P, possibly reflecting a more general tendency of clustered lipids for insertion into ordered domains. These results support a model for the description of the lateral organization of PIPs in cellular membranes, where both divalent cation interaction and membrane order are key modulators defining the lateral organization of these lipids.
Permanent Link: http://hdl.handle.net/11104/0276808