Role of Phosphoinositides in Cellular Signaling, Functions and Diseases

Mandal, Kalpana

doi:10.20944/preprints202009.0513.v1

2020

DOI: 10.20944/preprints202009.0513.v1

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Role of Phosphoinositides in Cellular Signaling, Functions and Diseases

Kalpana Mandal¹

Abstract: In this review we summarize the recent development in understanding the role of PIP2 in cellular function and signaling. We first discuss the effect of PIP2 on actin binding proteins addressing the mechanism of the actin cytoskeletal dynamics such as polymerization or depolymerization of the filamentous network or the coupling to membrane to generate forces. Next, we outline the role of PIP2 in membrane dynamics. We summarized how the membrane organization depends upon PIP2 in the presence of ions or transmemb… Show more

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Cited by 1 publication

References 106 publications

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Molecular mechanisms of spontaneous curvature and softening in complex lipid bilayer mixtures

Lessen

Sapp

Beaven

et al. 2022

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Membrane reshaping is an essential biological process. The chemical composition of lipid membranes determines their mechanical properties, and thus the energetics of their shape. Hundreds of distinct lipid species make up native bilayers, and this diversity complicates efforts to uncover what compositional factors drive membrane stability in cells. Simplifying assumptions, therefore, are used to generate quantitative predictions of bilayer dynamics based on lipid composition. One assumption commonly used is that "per lipid" mechanical properties are both additive and constant---that they are an intrinsic property of lipids independent of the surrounding composition. Related to this, is the assumption that lipid bulkiness, or "shape" determines its curvature preference, independently of context. In this study, all-atom molecular dynamics simulations on three separate multi-lipid systems were used to explicitly test these assumptions, applying methodology recently developed to isolate properties of single lipids or nanometer-scale patches of lipids. The curvature preference of populations of lipid conformations were inferred from their redistribution on a dynamically fluctuating bilayer. Representative populations were extracted by both structural similarity and semi-automated hidden Markov model analysis. The curvature preferences of lipid dimers were then determined and compared to an additive model that combines the monomer curvature prefer- ence of both the individual lipids. In all three systems, we identified conformational subpopulations of lipid dimers that showed non-additive curvature preference, in each case mediated by a special chemical interaction (e.g., hydrogen bonding). Our study highlights the importance of specific chemical interactions between lipids in multicomponent bilayers and the impact of interactions on bilayer stiffness. We identify two mechanisms of bilayer softening: Diffusional softening, which is driven by the dynamic coupling between lipid distributions and membrane undulations, and conformational softening, which is driven by the inter-conversion between distinct dimeric conformations.

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Molecular mechanisms of spontaneous curvature and softening in complex lipid bilayer mixtures

Lessen

Sapp

Beaven

et al. 2022

Preprint

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Role of Phosphoinositides in Cellular Signaling, Functions and Diseases

Cited by 1 publication

References 106 publications

Molecular mechanisms of spontaneous curvature and softening in complex lipid bilayer mixtures

Molecular mechanisms of spontaneous curvature and softening in complex lipid bilayer mixtures

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