Recent progress on lipid lateral heterogeneity in plasma membranes: From rafts to submicrometric domains

Abstract

The concept of transient nanometric domains known as lipid rafts has brought interest to reassess the validity of the Singer-Nicholson model of a fluid bilayer for cell membranes. However, this new view is still insufficient to explain the cellular control of surface lipid diversity or membrane deformability. During the past decade, the hypothesis that some lipids form large (submicrometric/mesoscale vs nanometric rafts) and stable (> min vs sec) membrane domains has emerged, largely based on indirect methods. Morphological evidence for stable submicrometric lipid domains, well-accepted for artificial and highly specialized biological membranes, was further reported for a variety of living cells from prokaryotes to yeast and mammalian cells. However, results remained questioned based on limitations of available fluorescent tools, use of poor lipid fixatives, and imaging artifacts due to non-resolved membrane projections. In this review, we will discuss recent evidence generated using powerful and innovative approaches such as lipid-specific toxin fragments that support the existence of submicrometric domains. We will integrate documented mechanisms involved in the formation and maintenance of these domains, and provide a perspective on their relevance on membrane deformability and regulation of membrane protein distribution.

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

“…As a matter of fact, RBC PM exhibits a particularly high cholesterol level (~45 mol%) in comparison to other cell types (e.g. ~35 mol% in CHO cells or ~15 mol% in fibroblasts) [9]. Yet, this small lipid plays key roles in membrane by regulating fluidity, lipid phase separation, mechanic resistance and membrane permeability [10].…”

Plasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins

“…However, there is a significant amount of controversy surrounding this topic (56,57). CAAX domains with polybasic residues are often used to target domains outside of rafts, whereas the Lyn domain is used to target rafts (58).…”

Cholesterol and nicotinic acetylcholine receptor: An intimate nanometer-scale spatial relationship spanning the billion year time-scale

“…Furthermore, fluorescent cholesterol probes can partition differentially in the plasma membrane as compared to the endogenous lipids [30]. Better extrinsic cholesterol probes, such as BODIPY-cholesterol, or the photoactivatable Ever-Fluor-fluorescein cholesterol have appeared in recent years (reviewed in S72 F.J. Barrantes / Cholesterol-receptor interactions [30,149]) but the essential difficulties associated with the bulky fluorophores still remain. In other words, the ideal extrinsic cholesterol probe -the bona fide qualitative tracer of ref.…”

“…In other words, the ideal extrinsic cholesterol probe -the bona fide qualitative tracer of ref. [30] for biophysical studies having a non-perturbing reporter group is still not available. For all these reasons other methodologies are needed to identify cholesterol recognition motifs in hormone or neurotransmitter receptors and ion channels without perturbing the sterol recognition region of these proteins.…”