Cytoskeletal interactions

Only a very small reduction in the number of acid-insoluble SH-groups in platelets was seen in the presence of feverfew extract [52]. A change in the high molecular weight protein pattern was only seen after the platelets had been activated. Such changes are indicative of polymerization of the proteins and the formation of S-S bridges and this can lead to disturbances in membrane-cytoskeletal interactions. Uptake of [ " C]arachidonic acid into phospholipids was inhibited by feverfew [53], which may be a result of altered cytoskeletal-membrane interaction. 

Feverfew extract was shown to inhibit deposition, aggregate formation and spreading of platelets on collagen fibres [54]. Changes in membrane-cytoskeletal interaction leading to a change in expression of membrane receptors involved in these processes may explain this result. Feverfew extract was further able to protect the endothelial monolayer in rabbit aortas from perfusion injury and some reversible increase in cAMP levels in the aorta segments was found [55]. 

As for the first question cytoskeletal interactions are apparently involved in keeping the proteinases and their transmembrane substrates apart, keeping them in distinct domains of the plasma membrane. See also ref. 15. Upon activation, the cytoskeletal attachments seem to be loosened so that the proteinases and their substrates can approach each other and interact. How spatial restriction and compartmentalization of enzymes and substrates controls their action is of more general importance. We shall come back to that (Chapter 7). 

Schmidt CE, Horwitz AF, Lautfenburger DA et al (1993) In-tegrin-cytoskeletal interactions in migrating fibroblasts are dynamic, asymmetric, and regulated. J Cell Biol 123 977-991... 

The cytoplasmic domain of P-selectin contains signals that mediate its rapid en-docytosis in clathrin-coated pits. Interactions of the cytoplasmic domain of P-selectin with these structures were found to enhance its adhesive function under flow [47]. Transfected CHO cells were prepared that express wild-type P-selectin or P-selectin constructs with substitutions or deletions in the cytoplasmic domain that either increase or decrease its internalization rate. Under flow, neutrophils tether equivalently to all constructs when expressed at matched densities. However, neutrophils roll on the internalization-competent constructs with greater adhesive strength, at slower velocities, and with more uniform motion. Confocal immunofluorescence microscopy demonstrates colocalization of a-adaptin, a component of clathrin-coated pits, with wild-type P-selectin but not with internalization-defective P-selectin lacking the cytoplasmic domain. Thus, interactions of P-selectin with clathrin-coated pits provide an alternative to cytoskeletal interactions to enhance adhesive function. The association of P-selectin with clathrin-coated pits may delay dissociation of P-selectin-PSGL-1 bonds and/or prevent forced extraction of P-selectin from the membrane. 

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