The Composition and Architecture of Membranes:- Sphingolipids and Cholesterol Cluster Together in Membrane Rafts

We have seen that diffusion of membrane lipids from one bilayer leaflet into the other is very slow unless cat alyzed, and that the different lipid species of the plasma membrane are asymmetrically distributed in the two leaflets of the bilayer (Fig. 11–5). Even within a single leaflet, the lipid distribution is not random. Glycosphingolipids (cerebrosides and gangliosides), which typically contain long-chain saturated fatty acids, form transient clusters in the outer leaflet that largely exclude glycerophospholipids, which typically contain one unsaturated fatty acyl group and a shorter saturated fatty acyl group. The long, saturated acyl groups of sphingolipids can form more compact, more stable associations with the long ring system of cholesterol than can the shorter, often unsaturated, chains of phospholipids. The cholesterol sphingolipid microdomains in the outer monolayer of the plasma membrane, visible with atomic-force microscopy (Box 11–1), are slightly thicker and more ordered (less fluid) than neighboring microdomains rich in phospholipids (Fig. 11–20) and are more difficult to dissolve with nonionic detergents; they behave like liquid-ordered sphingolipid rafts adrift in a sea of liquid-disordered phospholipids. These lipid rafts are remarkably enriched in two classes of integral membrane proteins: those anchored to the membrane by two covalently attached long-chain saturated fatty acids (two palmitoyl groups or a palmitoyl and a myristoyl group) and GPI-anchored proteins (Fig. 11–14). Presumably these lipid anchors, like the acyl chains of sphingolipids, form more stable associations with the cholesterol and long acyl groups in rafts than with the surrounding phospholipids. (It is notable that other lipid-linked proteins, those with covalently attached isoprenyl groups such as farnesyl, are not preferentially associated with the outer leaflet of sphingolipid/cholesterol rafts (Fig. 11–20a).) The “raft” and “sea” domains of the plasma membrane are not rigidly separated; membrane proteins can move into and out of lipid rafts on a time scale of seconds. But in the shorter time scale (microseconds) more relevant to many membrane-mediated biochemical processes, many of these proteins reside primarily in a raft. We can estimate the fraction of the cell surface occupied by rafts from the fraction of the plasma mem brane that resists detergent solubilization, which can be as high as 50% in some cases: the rafts cover half of the ocean (Fig. 11–20b). Indirect measurements in cultured fibroblasts suggest a diameter of roughly 50 nm for an individual raft, which corresponds to a patch containing a few thousand sphingolipids and perhaps 10 to 50 membrane proteins. Because most cells express more than 50 different kinds of plasma membrane proteins, it is likely that a single raft contains only a subset of mem brane proteins and that this segregation of membrane proteins is functionally significant. For a process that involves interaction of two membrane proteins, their presence in a single raft would hugely increase the likelihood of their collision. Certain membrane receptors and signaling proteins, for example, appear to be segregated together in membrane rafts. Experiments show that signaling through these proteins can be disrupted by manipulations that deplete the plasma mem brane of cholesterol and destroy lipid rafts. brane that resists detergent solubilization, which can be as high as 50% in some cases: the rafts cover half of the ocean (Fig. 11–20b). Indirect measurements in cultured fibroblasts suggest a diameter of roughly 50 nm for an individual raft, which corresponds to a patch containing a few thousand sphingolipids and perhaps 10 to 50 membrane proteins. Because most cells express more than 50 different kinds of plasma membrane proteins, it is likely that a single raft contains only a subset of mem brane proteins and that this segregation of membrane proteins is functionally significant. For a process that involves interaction of two membrane proteins, their presence in a single raft would hugely increase the likelihood of their collision. Certain membrane receptors and signaling proteins, for example, appear to be segregated together in membrane rafts. Experiments show that signaling through these proteins can be disrupted by manipulations that deplete the plasma mem brane of cholesterol and destroy lipid rafts.

FIGURE 11–20 Microdomains (rafts) in the plasma membrane. (a) Stable associations of sphingolipids and cholesterol in the outer leaflet produce a microdomain, slightly thicker than other membrane regions, that is enriched with specific types of membrane proteins. GPI-linked proteins are commonly found in the outer leaflet of such rafts, and proteins with one or several covalently attached long-chain acyl groups are common in the inner leaflet. Caveolin is especially common in inwardly curved rafts called caveolae (see Fig. 11–21). Proteins with attached prenyl groups (such as Ras; see Fig. 12–6) tend to be excluded from rafts. (b) The greater thickness of raft regions can be visualized by atomic force microscopy (see Box 11–1). In this view of a membrane region, we can see the rafts protruding from a lipid bilayer ocean; in the rafts, sharp peaks represent GPI-linked proteins. Note that these peaks are found almost exclusively in rafts.

اخر الاخبار

اخبار العتبة العباسية المقدسة

ماذا تعرف عن الهوية البصرية لمصحف النجف الأشرف؟

قسم شؤون المعارف يدعو الشباب إلى اقتناء كتاب نهج البلاغة لما يحتويه من مضامين علمية وثقافية

الهيأة العليا لإحياء التراث: التحقيق الجديد لكتاب نهج البلاغة أُجري على وَفقِ أسس علمية دقيقة

مركز التراث الإسلامي: التحقيق الجديد لكتاب نهج البلاغة تمّ عَبرَ عشر نسخ نفيسة لكبار العلماء من القرن الخامس إلى الثامن الهجري

المزيد

الآخبار الصحية

خبير يكشف 5 حقائق طبية صادمة وغير معروفة

ليس الأسود ولا الحيتان.. "كائن صغير" هو أخطر قاتل للبشر!

بارقة أمل لمرضى "الإيدز".. علاج خلوي ينجح في كبح الفيروس

ظاهرة مقلقة تتوسع.. "المستنشقات" خطر صامت يهدد المراهقين

المزيد

الآخبار التكنلوجية

اكتشاف مادة في الثوم تحسن قوة العضلات وتبطئ شيخوختها

تطور الحياة على الأرض المبكرة اعتمد على معدن نادر

باحثون صينيون يطوّرون بطارية مائية قد تعمل 300 عام

الذكاء الاصطناعي..هل يصبح متهما جنائيا في الجرائم والانتحار؟

المزيد

مواضيع ذات صلة

Solute Transport across Membranes:- Transporters Can Be Grouped into Superfamilies Based on Their Structures

Solute Transport across Membranes:- Passive Transport Is Facilitated by Membrane Proteins

Membrane Dynamics:- Membrane Fusion Is Central to Many Biological Processes

The Composition and Architecture of Membranes:- Peripheral Membrane Proteins Are Easily Solubilized

The Composition and Architecture of Membranes:- A Lipid Bilayer Is the Basic Structural Element of Membranes

Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins:- Cooperative Ligand Binding Can Be Described

Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins:- Hemoglobin Undergoes a Structural Change on Binding Oxygen

Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins:- Hemoglobin Subunits Are Structurally Similar to Myoglobin

Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins: -Oxygen Is Transported in Blood by Hemoglobin

Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins:- Protein Structure Affects How Ligands Bind

Membrane Dynamics:- Transbilayer Movement of Lipids Requires Catalysis

The Composition and Architecture of Membranes:- Lipids and Proteins Diffuse Laterally in the Bilayer