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- W2515668738 abstract "The interdependence of the signalling pathways, which culminate in secretion and rearrangement of the actin cytoskeleton has been extensively studied. To date such a link has proved controversial. Here I have investigated whether such a link exists in rat peritoneal mast cells (RPMC), using both intact and streptolysin-O permeabilised cells. This work has utilised the properties of a recently discovered marine toxin - latrunculin, which has been shown to depolymerise F-actin. This toxin was found to induce a dose dependent reduction in F-actin, which was clearly paralleled, by a reduction in secretory responsiveness. The findings indicate that the signalling pathways from the receptor, but not the final steps of exocytosis, require cytoskeletal rearrangements. This study revealed a very interesting, previously unreported, effect of latrunculin. The shift in the F-: G-actin equilibrium induced by this toxin induces a relocalisation of actin into the nucleus. This effect of latrunculin was investigated and found to dependent on the actin-binding protein cofilin. Following this work a detailed study of the localisation and regulation of mast cell actin revealed the existence of a previously undiscovered pool of monomeric actin, lying within the nuclei of resting permeabilised RPMC. Further investigation showed that both ATP and G-proteins, which are known to simulate secretion, regulate this pool of actin. The results suggest that both ATP and G-proteins may control the localisation of this pool via cofilin. Many actin binding proteins, including cofilin, are widely acknowledged to be regulated by PIP2. Moreover phosphatidylinositol transfer protein (PI-TP), which has been shown to promote PIP2 synthesis, also enhances secretion. This study found that alpha isoform of PI-TP is involved in both the priming and final steps of exocytosis in RPMC. This role PI-TP however is only revealed in metabolically inhibited mast cells, i.e. those depleted of their endogenous PIP2." @default.
- W2515668738 created "2016-09-16" @default.
- W2515668738 creator A5004922464 @default.
- W2515668738 date "1999-01-01" @default.
- W2515668738 modified "2023-09-27" @default.
- W2515668738 title "Participation of the actin cytoskeleton in the secretory function of mast cells." @default.
- W2515668738 hasPublicationYear "1999" @default.
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