Extracellular membrane components

Retrieval of membrane components in the secretory pathway through receptor-mediated endocytosis (RME) is a clathrin-coat-dependent process [5]. The clathrin coat provides stability to the vesicle core and allows uptake of specific membrane proteins for reuse or degradation. RME shows a remarkable degree of specificity, allowing cells to internalize with astonishing efficiency only those selected molecules independent of their extracellular concentration. 

Figure 4.13. Model of peptide initiation of mast secretion. Insertion of the hydrophobic region of the peptide into the lipid bilayer properly orients the basic (+) groups at the N-terminus for binding to negatively charged membrane components. As a result, there is activation of the G protein complex with the subsequent generation of inositol triphosphate (IP ) and diacylglycerol (DAG). These intermediates then stimulate the mobilization of cellular Ca and possibly the transient influx of extracellular Ca as well as the activation ofprotein kinase C. As a consequence, the level of intracellular free ionized Ca is maintained at an elevated state. The end result is the exocytotic extrusion of secretory granules.

Sialyltransferase activity has also been described in plasma membranes from different cells, including blood platelets.285 The function of the enzyme on cell surfaces is unknown, as resialylation of membrane components directly on the cell surface is improbable, owing to the presence of CMP-Neu5Ac hydrolase in the plasma membrane, and the lack of CMP-sialic acids in the extracellular space. Furthermore, evidence has never been obtained for a role of cell-surface gly-cosyltransferases in cellular interaction according to a hypothesis of Roseman s.281... 

The transition from mesenchyme to epithelium involves biochemical changes in the cells and the extracellular matrix, N-CAM expression on cell surfaces disappears, replaced by L-CAM (uvomorulin). Vimentin, a characteristic cytoskeletal component of mesenchyme, disappears, and cytokeratin, characteristic of epithelia, appears. There is a decrease in collagen I extracellularly and an increase in the basement membrane components laminin and collagen IV. 

Berasain, P., Goni, F., McGonigle, S., Dowd, A., Dalton, J.P., Frangione, B. and Carmona, C. (1997) Proteinases secreted by Fasciola hepatica degrade extracellular matrix and basement membrane components. Journal of Parasitology 83, 1-5. 

Recent reviews pertaining to such topics as the role of calcium in growth control (82), lectins as natural membrane components (83), fibronectins (84), and biochemical studies of the cell cycle (85, 86, 87, 88), together with many of the works cited earlier, suggest a dynamic, time-dependent relationship between extracellular factors, membrane components and the intracellular metabolic machinery as a cell goes from... 

Phase I and II clinical trials indicated that acronycine reduced pain of the spine in some patients with multiple myeloma [280,282,283]. Acronycine has been reported to cause leukopoenia and to have CNS-depressant activity [284], Biochemically, acronycine inhibits incorporation of extracellular nucleosides into the RNA and DNA of leukaemia L-5178Y cell culture. There is, however, no evidence of interaction between acronycine and DNA or inhibition of template activity of DNA. This alkaloid does not inhibit nucleic acid synthesis in the cell, but rather inhibits the accumulation of extracellular uridine or thymidine, as nucleotides, in the intracellular precursor pool [285, 286], Acronycine, acting primarily on membranous organelles [287], seems to interfere with the structure, function and/or turnover of cell membrane components, thereby changing the fluidity of the plasma membrane [288]. 

Other processes that lead to nonlinear compartmental models are processes dealing with transport of materials across cell membranes that represent the transfers between compartments. The amounts of various metabolites in the extracellular and intracellular spaces separated by membranes may be sufficiently distinct kinetically to act like compartments. It should be mentioned here that Michaelis-Menten kinetics also apply to the transfer of many solutes across cell membranes. This transfer is called facilitated diffusion or in some cases active transport (cf. Chapter 2). In facilitated diffusion, the substrate combines with a membrane component called a carrier to form a carrier-substrate complex. The carrier-substrate complex undergoes a change in conformation that allows dissociation and release of the unchanged substrate on the opposite side of the membrane. In active transport processes not only is there a carrier to facilitate crossing of the membrane, but the carrier mechanism is somehow coupled to energy dissipation so as to move the transported material up its concentration gradient. 

Vukicevic, S. et al. 1992. Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular activity related to extracellular matrix components. Exp. Cell Res. 202, 1-8. 

The studies reported here using the isolated, vascularly perfused rat intestine system and isolated brush border membrane vesicles fail to support a role for a specific zinc-binding ligand involved in zinc uptake in the rat. Rather, the extent of zinc uptake involves the interaction of several phenomena, including both extracellular and intracellular reactions. It appears that the major pathway of zinc uptake under normal dietary conditions involves the transfer of zinc from various dietary components to a carrier mediated transport system at the brush border membrane. The net absorption of zinc from the lumen could involve a competition between various dietary components, zinc binding ligands and the membrane carrier for zinc. Thus, in some cases, those compounds in the lumen with a higher affinity for zinc than the membrane component will be less likely to permit transfer of zinc to the carrier, while compounds with a lower affinity for zinc will increase the amount of zinc made... 

---