Abstract

Calcium ions (Ca2+) are major messengers in cell signaling, impacting nearly every aspect of cellular life. Those signals are generated within a wide spatial and temporal range through a large variety of Ca2+ channels, pumps, and exchangers. More and more evidences suggest that Ca2+ exchanges are regulated by their surrounding lipid environment. In this review, we point out the technical challenges that are currently being overcome and those that still need to be defeated to analyze the Ca2+ transport protein–lipid interactions. We then provide evidences for the modulation of Ca2+ transport proteins by lipids, including cholesterol, acidic phospholipids, sphingolipids, and their metabolites. We also integrate documented mechanisms involved in the regulation of Ca2+ transport proteins by the lipid environment. Those include: (i) Direct interaction inside the protein with non-annular lipids; (ii) close interaction with the first shell of annular lipids; (iii) regulation of membrane biophysical properties (e.g., membrane lipid packing, thickness, and curvature) directly around the protein through annular lipids; and (iv) gathering and downstream signaling of several proteins inside lipid domains. We finally discuss recent reports supporting the related alteration of Ca2+ and lipids in different pathophysiological events and the possibility to target lipids in Ca2+-related diseases.

Highlights

  • Membranes provide interfaces that separate two aqueous environments and contribute to several functions, including regulation of solute exchanges, signal transduction, lipid metabolism, and membrane fusion and fission

  • Transient receptor potential (TRP) channels are a group of non-selective cation channels activated by a large panel of stimuli and that are expressed mostly at the PM of numerous cell types

  • Piezo1 channel is highly dependent on its surrounding lipid packing environment which can be modulated by dietary fatty acids, as recently demonstrated by Vásquez et al They showed that margaric acid inhibits Piezo1 activation by increasing membrane bending stiffness while long chain polyunsaturated fatty acids modulate channel inactivation by decreasing membrane bending stiffness [294]

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Summary

Introduction

Membranes provide interfaces that separate two aqueous environments and contribute to several functions, including regulation of solute exchanges, signal transduction, lipid metabolism, and membrane fusion and fission. Those approaches have to present a high resolution and interaction between proteins and the surrounding lipids Those approaches have to present a high to be compatible live cell imaging reasons:. Such equipment allows to integrate sample analysis at both the cellular and molecular levels It should be more efficient than LSCM for a number of applications related to dynamic live cell imaging, such as ratio imaging, FRAP (Förster recovery after photobleaching) and FRET (fluorescence resonance energy transfer; see Section 2.1.2). Another difficulty, besides the imaging approaches, is the limitation of reliable fluorescent tools for membrane lipid imaging. Binding domains, or nanobodies (for a review on these different classes of probes, see [16])

Förster Resonance Energy Transfer
Reconstitution
Membrane Protein Structural Biology and Mass Spectrometry
Molecular Simulation
Ca in the Cytosol
Transient Receptor Potential Channels
Voltage-Gated Channels
Mechanosensitive Ion Channels
Direct Interaction with Non-Annular Lipids
Close Interaction with the First Shell of Annular Lipids
Membrane Lipid Packing
Membrane Thickness
Membrane
Illustration
Conclusions and Challenges for the Future
Findings
Methods
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