Submembrane cytoskeleton

The membrane cytoskeleton (inclusive of the submembranous actin-spec-trin network) may function in the establishment and maintenance of restricted domains of specific proteins on the plasma membrane of polarized epithelial cells (Rodriguez-Boulan and Nelson, 1989 Mays et al., 1994). 

Spectrin is a common component of the submembranous cytoskeleton. It was first identified as a major constituent of the erythrocyte membrane cytoskeleton, but has since been found in many other vertebrate tissues as well as in the nonvertebrates Drosophila, Acanthamoeba, Dictyostelium, and echinoderms (Bennett and Condeelis, 1988 Byers et al., 1992 Dubreuil et al., 1989 Pollard, 1984 Wessel and Chen., 1993). The ease with which spectrin could be isolated from erythrocyte ghosts made it an ideal candidate for the study of the biochemical processes involved in the assembly and organization of the cytoskeleton (Gratzer, 1985). 

The membrane skeleton acts as an elastic semisolid, allowing brief periods of deformation followed by reestablishment of the original cell shape (reviewed by Bennett and Gilligan, 1993). Erythrocytes in the human bloodstream have to squeeze repeatedly through narrow capillaries of diameters smaller than their own dimensions while resisting rupture. A functional erythrocyte membrane is pivotal to maintaining the functional properties of the erythrocyte. This importance is apparent when examination is made of many hemolytic anemias, where mutation of proteins involved in the structure of the submembranous cytoskeleton, and its attachment to the lipid bilayer, result in a malformed or altered cytoskeletal architecture and a disease phenotype. 

Erythrocytes are small compared with most other cells and are peculiar because of their biconcave disk shape (see Fig. 1-12). They have no nucleus, because it is extruded just before the release of the cell into the blood stream from the bone marrow, where the cells develop. Their cytoplasm has no organelles and is full of the protein hemoglobin that binds 02 and C02. In the cytoplasm are other proteins also, namely, (1) the submembrane cytoskeleton, (2) enzymes of the glycolytic and... 

In platelets, signaling is initiated primarily through members of the heterotrimeric G protein-coiqtled femily of leceptois (seven transmembrane domains) and through adhesion receptors, and the signaling involves activation of both Ser/Thr kinases and tyrosine kinases. Neither G protein-coiqtled receptors nor adhesion receptors have intrinsic tyrosine kinase activity. However, NRTKs (with SH2-, SH3-, and proline-rich domains) are activated and initiate tyrosine phosphorylation reactions that in turn lead to the recmitment of signaling molecules to certain locations in the cell. These tyrosine kinases may phosphorylate submembranous proteins including receptors for cytoplasmic domains or components of the submembranous cytoskeleton of adhesion receptor-cytoskeleton... 

ERM proteins belong to the band 4.1 superfamily, which also includes the tumor suppressor merlin ERM proteins share three highly conserved structural domains. The N-terminal PERM (/our-point one, ezrin, radixin, moesin) domain binds directly or indirectly to membrane proteins, whereas the C-terminal domain binds F-actin, resulting in actin filament rearrangement. ERM proteins therefore act as cross-linkers between cell membrane proteins and the actin cytoskeleton. The N- and C-terminal domains are linked by an a-helical coiled domain that modulates ERM actions ERM proteins are located in the cytoplasm in a dormant state due to inhibitory interactions between their N- and C-domains. They are activated by phosphorylation and/or interactions with phospholipids, whereupon they move to a submembranous location. 

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