Cytoskeleton ankyrin

Mechanical functions of cells require interactions between integral membrane proteins and the cytoskeleton 29 The spectrin-ankyrin network comprises a general form of membrane-organizing cytoskeleton within which a variety of membrane-cytoskeletal specializations are interspersed 29 Interaction of rafts with cytoskeleton is suggested by the results of video microscopy 29... 

In erythrocytes and most other cells, the major structural link of plasma membranes to the cytoskeleton is mediated by interactions between ankyrin and various integral membrane proteins, including Cf/HCOj antiporters, sodium ion pumps and voltage-dependent sodium ion channels. Ankyrin also binds to the =100 nm, rod-shaped, antiparallel a(3 heterodimers of spectrin and thus secures the cytoskeleton to the plasma membrane. Spectrin dimers self-associate to form tetramers and further to form a polygonal network parallel to the plasma membrane (Fig. 2-9D). Neurons contain both spectrin I, also termed erythroid spectrin, and spectrin II, also termed fodrin. Spectrin II is found throughout neurons, including axons, and binds to microtubules, whereas spectrin I occurs only in the soma and dendrites. 

The cytoskeleton is found near the axonal membrane and consists of microfilaments linked internally to microtubules and the plasma membrane by a network of filamentous protein that includes the brain-specific protein fodrin. This protein forms attachment sites for integral membrane proteins either by means of the neuronal cell adhesion molecule (N-CAM) or indirectly by means of a specific protein called ankyrin in the case of the sodium channels. This may provide a means whereby the sodium channels are concentrated in the region of the nodes of Ranvier. Thus the cortical cytoskeleton plays a vital role in neuronal function by acting as an attachment site for various receptors and ion channels, but also for s)maptic vesicles at nerve terminals, thereby providing a mechanism for concentrating the vesicles prior to the release of the neurotransmitter. 

What is the function of the membrane skeleton There is a group of hereditary diseases including spherocytosis in which erythrocytes do not maintain their biconcave disc shape but become spherical or have other abnormal shapes and are extremely fragile.269 272 Causes of spherocytosis include defective formation of spectrin tetramers and defective association of spectrin with ankyrin or the band 4.1 protein.265 273 Thus, the principal functions of these proteins in erythrocytes may be to strengthen the membrane and to preserve the characteristic shape of erythrocytes during their 120-day lifetime in the bloodstream. In other cells the spectrins are able to interact with microtubules, which are absent from erythrocytes, and to microtubule-associated proteins of the cytoskeleton (Chapter 7, Section F).270 In nerve terminals a protein similar to erythrocyte protein 4.1 may be involved in transmitter release.274 The cytoskeleton is also actively involved in transmembrane signaling. 

The structure of spectrin and the location of spectrin in the cytoskeleton. (a) An a/3 dimer of spectrin. Both a and f3 subunits are extended structures consisting of end-to-end domains of 106 amino-acyl residues folded into three a helices the subunits twist about one another loosely as shown. (b) The erythrocyte membrane skeleton. Spectrin tetramers ((X2P2), shown in yellow, are linked to the cytoplasmic domain of the anion channel (blue) by the protein ankyrin (red), and to glycophorin and actin filaments by protein 4.1. This structure lends stability to the red cell membrane while maintaining sufficient flexibility to allow erythrocytes to withstand substantial shear forces in the peripheral circulation. 

The integral membrane proteins glycophorin and anion exchange protein are components in a network of linkages that connect the plasma membrane to structural elements of the cytoskeleton (e.g., actin, spectrin, protein 4.1, and ankyrin). 

A FIGURE 5-31 Cortical cytoskeleton supporting the plasma membrane in human erythrocytes, (a) Electron micrograph of the erythrocyte membrane showing the spoke-and-hub organization of the cytoskeleton. The long spokes are composed mainly of spectrin and can be seen to intersect at the hubs, or membrane-attachment sites. The darker spots along the spokes are ankyrin molecules, which cross-link spectrin to... 

The red cell membrane must be highly deformable to allow it to travel throughout the capillary system in the body. This is because of a complex cytoskeletal structure that consists of the major proteins spectrin, ankyrin, and band 3 protein Mutations in these proteins lead to improper formation of the membrane cytoskeleton, ultimately resulting in malformed red cells, spherocytes, in the circulation. Spherocytes have a shortened life span, leading to loss of blood cells. 

The surface area of the red cell is approximately 140 p,m, which is greater than the surface of a sphere needed to enclose the contents of the red cell (98 p,m ). The presence of this extra membrane and the cytoskeleton that supports it allows the red cell to be stretched and deformed by mechanical stresses as the cell passes through narrow vascular beds. On the cytoplasmic side of the membrane, proteins form a two-dimensional lattice that gives the red cell its flexibility (Fig. 44.10). The major proteins are spectrin, actin, band 4.1, band 4.2, and ankyrin. Spectrin, the major protein, is a heterodimer composed of a and (3 subunits wound around each other. The dimers self-associate at the heads. At the opposite end of the spectrin dimers, actin and band 4.1 bind near to each other. Multiple spectrins can bind to each actin filament, resulting in a branched membrane cytoskeleton. 

The spectrin cytoskeleton is connected to the membrane lipid bilayer by ankyrin, which interacts with (3-spectrin and the integral membrane protein, band 3. Band 4.2 helps to stabilize this connection. Band 4.1 anchors the spectrin skeleton with the membrane by binding the integral membrane protein glycophorin C and the actin complex, which has bound multiple spectrin dimers. 

Fig. 44.10. A generalized view of the erythrocyte cytoskeleton. A. The major protein, spectrin, is linked to the plasma membrane either through interactions with ankyrin and band 3, or with actin, band 4.1, and glycophorin. Other proteins in this complex, but not shown, are tropomyosin and adducin. B. A view from inside the cell, looking up at the cytoskeleton. This view displays the cross-linking of the sprectrin dimers to actin and band 3 anchor sites.

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