Cell membranes surface receptors role

More general information about the potential role of apoE in cellular lipoprotein uptake has come from studies with cultured cells (e.g., fibroblasts). Such cells manifest surface receptors for LDL that bind apoB, the protein component of LDL. This is followed by receptor-mediated endocytosis, fusion of the endo-cytic vesicles with lysosomes, and LDL degradation within the lysosomes (see Goldstein and Brown, 1979 Brown et al., 1981, for reviews and references). Cholesteryl esters taken into cells in this manner are hydrolyzed by a lysosomal acid lipase. The liberated cholesterol then leaves the lysosome and is used in the cell for membrane synthesis and as a regulator of intracellular cholesterol homeostasis. 

Caveolae are invaginations of the plasma membrane. They contain the protein caveolin and are rich in certain phospholipids. Similar to coated pits, they bud off internally forming endocytic vesicles. Caveolae play an important role in the internalization of certain cell surface receptors. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

The protein kinase family encompasses more than three hundred members of critically important enzymes, each one with a specific role or function within the cell. These enzymes, ATP-phosphotransferases, recognize target proteins and through the phosphorylation of specific sites either activate or deactivate a particular pathway of signal transduction. Many of these signaling pathways are associated with cell surface receptors, which are located in the membranes that surround cells. The difference between the families of protein kinases is that they have different targets and generally fall into two major classes ... 

It appears that insulin and certain growth factors may exert their effects by acting through this type of tyrosine kinase receptor-enzyme system.21,44 Insulin, for example, binds to the extracellular component of a protein located on skeletal muscle cells, thereby initiating activation of this protein s enzymatic activity on the inner surface of the cell membrane. This change in enzyme function causes further changes in cell activity, which ultimately result in increased glucose uptake in the muscle cell. The function of insulin receptors and their role in the cause and treatment of diabetes mellitus are discussed in more detail in Chapter 32. 

Numerous studies have pointed to an important role for cholesterol during proliferation and progression of cancer (e.g., ref. 612-615). Rapidly dividing cancer cells have two major routes to fulfill their need for cholesterol to form new cell membrane endogenous synthesis of cholesterol and/or receptor-mediated uptake of exogenous LDL particle-associated cholesterol and cholesterol esters (ref. 612,613,615). Each LDL particle contains a cholesterol ester core surrounded by a polar shell of phospholipids (primarily phosphoglycerides), free cholesterol, and apolipoprotein B (ref. 616-618). Once bound to its cell surface receptor, LDL is internalized by receptor-mediated endocytosis and degraded in lysosomes, and the subsequently released cholesterol may be used for membrane synthesis by the tumor (ref. 619). 

GSLs play crucial roles in functions of the nervous system and skin, cell growth and differentiation, infections, cancer, and immune response [1, 2, 12], Owing to their strategic position in membranes, they interact with toxins, bacteria, and viruses. They form membrane lipid rafts and present the attached carbohydrates as cell-surface receptors and, thus, serve as portals of entry for pathogens through carbohydrate-protein interactions [13]. For example, HIV entry is mediated by GalCer receptors of the host cells [14],... 

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