Editing Red blood cell (section)

====Membrane lipids====
[[Image:Erythrocyte Membrane lipids.jpg|thumb|250px|The most common red blood cell membrane lipids, schematically disposed as they are distributed on the bilayer. Relative abundances are not at scale.]]
The red blood cell membrane comprises a typical [[lipid bilayer]], similar to what can be found in virtually all human cells. Simply put, this lipid bilayer is composed of [[cholesterol]] and [[phospholipid]]s in equal proportions by weight. The lipid composition is important as it defines many physical properties such as membrane permeability and fluidity. Additionally, the activity of many membrane proteins is regulated by interactions with lipids in the bilayer.

Unlike cholesterol, which is evenly distributed between the inner and outer leaflets, the 5 major phospholipids are asymmetrically disposed, as shown below:

'''Outer monolayer'''
* [[Phosphatidylcholine]] (PC);
* [[Sphingomyelin]] (SM).

'''Inner monolayer'''
* [[Phosphatidylethanolamine]] (PE);
* [[Phosphoinositol]] (PI) (small amounts).
* [[Phosphatidylserine]] (PS);

This asymmetric phospholipid distribution among the bilayer is the result of the function of several energy-dependent and energy-independent [[phospholipid]] transport proteins. Proteins called "[[Flippase]]s" move phospholipids from the outer to the inner monolayer, while others called "[[floppase]]s" do the opposite operation, against a concentration gradient in an energy-dependent manner. Additionally, there are also "[[scramblase]]" proteins that move phospholipids in both directions at the same time, down their concentration gradients in an energy-independent manner. There is still considerable debate ongoing regarding the identity of these membrane maintenance proteins in the red cell membrane.

The maintenance of an asymmetric phospholipid distribution in the bilayer (such as an exclusive localization of PS and PIs in the inner monolayer) is critical for the cell integrity and function due to several reasons:
* [[Macrophages]] recognize and [[phagocytose]] red cells that expose PS at their outer surface. Thus the confinement of PS in the inner monolayer is essential if the cell is to survive its frequent encounters with macrophages of the [[reticuloendothelial system]], especially in the [[spleen]].
* Premature destruction of [[Thalassemia|thallassemic]] and sickle red cells has been linked to disruptions of lipid asymmetry leading to exposure of PS on the outer monolayer.
* An exposure of PS can potentiate adhesion of red cells to vascular endothelial cells, effectively preventing normal transit through the microvasculature. Thus it is important that PS is maintained only in the inner leaflet of the bilayer to ensure normal blood flow in microcirculation.
* Both PS and [[phosphatidylinositol 4,5-bisphosphate]] (PIP2) can regulate membrane mechanical function, due to their interactions with skeletal proteins such as [[spectrin]] and [[Band 4.1|protein 4.1R]]. Recent studies have shown that binding of spectrin to PS promotes membrane mechanical stability. PIP2 enhances the binding of [[Band 4.1|protein band 4.1R]] to [[glycophorin C]] but decreases its interaction with [[Band 3|protein band 3]], and thereby may modulate the linkage of the bilayer to the membrane skeleton.

The presence of specialized structures named "[[lipid rafts]]" in the red blood cell membrane have been described by recent studies. These are structures enriched in [[cholesterol]] and [[sphingolipids]] associated with specific membrane proteins, namely [[FLOT1|flotillin]]s, [[STOM]]atins (band 7), [[G-proteins]], and [[Beta-adrenergic receptor|β-adrenergic receptor]]s. [[Lipid rafts]] that have been implicated in cell signaling events in nonerythroid cells have been shown in erythroid cells to mediate [[Beta-adrenergic receptor|β2-adregenic receptor]] signaling and increase [[Cyclic adenosine monophosphate|cAMP]] levels, and thus regulating entry of [[malaria]]l parasites into normal red cells.<ref name="Mohandas2008">{{cite journal | vauthors = Mohandas N, Gallagher PG | title = Red cell membrane: past, present, and future | journal = Blood | volume = 112 | issue = 10 | pages = 3939–3948 | date = November 2008 | pmid = 18988878 | pmc = 2582001 | doi = 10.1182/blood-2008-07-161166 }}</ref><ref>{{cite journal | vauthors = Rodi PM, Trucco VM, Gennaro AM | title = Factors determining detergent resistance of erythrocyte membranes | journal = Biophysical Chemistry | volume = 135 | issue = 1–3 | pages = 14–18 | date = June 2008 | pmid = 18394774 | doi = 10.1016/j.bpc.2008.02.015 | hdl-access = free | hdl = 11336/24825 }}</ref>