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Participation of the actin cytoskeleton in the secretory function of mast cells

Pendelton, Annmarie; (1999) Participation of the actin cytoskeleton in the secretory function of mast cells. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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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.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Participation of the actin cytoskeleton in the secretory function of mast cells
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Mast cells
URI: https://discovery.ucl.ac.uk/id/eprint/10107098
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