Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(Dense Granule Secretion). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


Temple University

1. Chari, Ramya. Molecular Mechanisms Underlying Differential Regulation of Platelet Dense Granule Secretion by Protein Kinase C delta.

Degree: PhD, 2010, Temple University

Physiology

Protein Kinase C delta (PKCδ) is expressed in platelets and activated downstream of protease-activated receptors (PAR)s and glycoprotein VI (GPVI) receptors. We evaluated the role of PKCδ in platelets using two approaches - pharmacological and molecular genetic approach. In human platelets pretreated with isoform selective antagonistic RACK peptide (δV1-1)TAT, and in the murine platelets lacking PKCδ, PAR4-mediated dense granule secretion was inhibited, whereas GPVI-mediated dense granule secretion was potentiated. These effects were statistically significant in the absence and presence of thromboxane A2 (TXA2). Furthermore, TXA2 generation was differentially regulated by PKCδ. However, PKCδ had a small effect on platelet P-selectin expression. Calcium- and PKC-dependent pathways independently activate fibrinogen receptor in platelets. When calcium pathways are blocked by dimethyl-BAPTA, AYPGKF-induced aggregation in PKCδ null mouse platelets and in human platelets pretreated with (δV1-1)TAT, was inhibited. In a FeCl3-induced injury in vivo thrombosis model, PKCδ-/- mice occluded similar to their wild-type littermates. Hence, we conclude that PKCδ differentially regulates platelet functional responses such as dense granule secretion and TXA2 generation downstream of PARs and GPVI receptors, but PKCδ deficiency does not affect the thrombus formation in vivo. We further investigated the mechanism of such differential regulation of dense granule release by PKCδ in platelets. SH2 domain-containing Inositol Phosphatase (SHIP)-1 is phosphorylated on Y1020, a marker for its activation, upon stimulation of human platelets with PAR agonists, SFLLRN and AYPGKF, or GPVI agonist, convulxin. GPVImediated SHIP-1 phosphorylation occurred rapidly at 15 sec whereas PAR-mediated phosphorylation was delayed, occurring at 1 min. Lyn and SHIP-1, but not SHIP-2 or Shc, preferentially associated with PKCδ upon stimulation of platelets with a GPVI agonists, but not with a PAR agonist. In PKCδ null murine platelets, convulxin-induced SHIP-1 phosphorylation was inhibited, suggesting that PKCδ regulates the phosphorylation of SHIP-1. Furthermore, in Lyn null murine platelets, GPVI-mediated phosphorylations on Y-1020 of SHIP-1, Y311 and Y155 of PKCδ were inhibited. In murine platelets lacking Lyn, or SHIP-1, GPVI-mediated dense granule secretions were potentiated, whereas PAR-mediated dense granule secretions were inhibited. Phosphorylated SHIP-1 associated with phosphorylated-Y155 PKCδ peptide. Therefore, we conclude that Lyn-mediated phosphorylations of PKCδ and SHIP-1 and their associations negatively regulate GPVI-mediated dense granule secretion in platelets.

Temple University – Theses

Advisors/Committee Members: Kunapuli, Satya P., Driska, Steven Paul, Eguchi, Satoru, Daniel, James L., Naik, Ulhas P..

Subjects/Keywords: Biology, Physiology; Biology, Cell; Biology, Molecular; Dense Granule Secretion; Phosphorylation; Platelets; Protein Kinase C; Signaling; Thrombosis

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Chari, R. (2010). Molecular Mechanisms Underlying Differential Regulation of Platelet Dense Granule Secretion by Protein Kinase C delta. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,77283

Chicago Manual of Style (16th Edition):

Chari, Ramya. “Molecular Mechanisms Underlying Differential Regulation of Platelet Dense Granule Secretion by Protein Kinase C delta.” 2010. Doctoral Dissertation, Temple University. Accessed October 21, 2020. http://digital.library.temple.edu/u?/p245801coll10,77283.

MLA Handbook (7th Edition):

Chari, Ramya. “Molecular Mechanisms Underlying Differential Regulation of Platelet Dense Granule Secretion by Protein Kinase C delta.” 2010. Web. 21 Oct 2020.

Vancouver:

Chari R. Molecular Mechanisms Underlying Differential Regulation of Platelet Dense Granule Secretion by Protein Kinase C delta. [Internet] [Doctoral dissertation]. Temple University; 2010. [cited 2020 Oct 21]. Available from: http://digital.library.temple.edu/u?/p245801coll10,77283.

Council of Science Editors:

Chari R. Molecular Mechanisms Underlying Differential Regulation of Platelet Dense Granule Secretion by Protein Kinase C delta. [Doctoral Dissertation]. Temple University; 2010. Available from: http://digital.library.temple.edu/u?/p245801coll10,77283


University of Oxford

2. Kroeger, Benjamin Robert. The genetic regulation and subcellular dynamics of secretory and endolysosomal organelles of Drosophila secondary cells.

Degree: PhD, 2017, University of Oxford

Secretory processes underpin the emergence of cellular diversity in complex multicellular organisms. However, our understanding of the basic mechanisms controlling the different secretory and endosomal compartments involved remains surprisingly incomplete. During my DPhil I have studied a specialised epithelial cell type in the male Drosophila accessory glands, the secondary cell, which contains unusually large intracellular compartments that are accessible to detailed morphological study. I characterise the organisation, ultrastructure and molecular composition of this cell's secretory and endosomal compartments, and I employ specific Rab GTPases, conserved coordinators of membrane trafficking and identity, to define multiple compartmental subtypes. By developing super-resolution and time-lapse microscopy approaches in these cells, I show that numerous intraluminal vesicles (ILVs) are formed within Rab11-labelled secretory compartments and released into the accessory gland lumen as exosomes, the first clear demonstration in eukaryotic cells of exosome biogenesis within a non-late endosomal compartment. Biogenesis of these ILVs is dependent on evolutionarily conserved Endosomal Sorting Complexes Required for Transport (ESCRT) 0-III genes and involves loading of compartment-specific cargoes. Work by others, some in collaboration with me, has shown that these novel mechanisms are conserved in human cells. I show that dense-core granules, the structures employed to package proteins and other molecules destined for regulated secretion, form within large non-cored Rab6- positive compartments, in a process that seems to involve inputs from both the Golgi and recycling endosomal pathways. Further analysis has revealed roles for specific Rabs, for ILVs, and for the conserved fibrillar protein Mfas/TGFBI in different aspects of DCG formation. I also show that DCGs are not only secreted, but can also be degraded by fusion to acidic endosomal compartments. Remarkably, there is evidence that mammalian cells may employ all of these mechanisms and defects in these processes may be linked to diseases like cancer, diabetes and neurodegenerative disorders. Hence my work has established a new system to study complex secretory mechanisms, which can now be developed to model specific disease processes in the future. In summary, I have discovered several novel cell biological mechanisms controlling exosome biology, dense-core granule biogenesis, regulated secretion, and endolysosomal trafficking. Some of these already appear relevant to human health and disease, suggesting that the secondary cell system has considerable further potential for unravelling the fundamental processes underlying eukaryotic secretion in the future.

Subjects/Keywords: 571.6; Cytology; Genetics; Microscopy; Drosophila; Exosome; 3D Structured Illumination Microscopy; Trafficking; Electron Microscopy; Endosome; Rab GTPase; Lysosome; Fluorescence Microscopy; Secretion; Dense-Core Granule

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Kroeger, B. R. (2017). The genetic regulation and subcellular dynamics of secretory and endolysosomal organelles of Drosophila secondary cells. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:dce9ae14-b03d-4fca-8429-de839cc40d6a ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.736126

Chicago Manual of Style (16th Edition):

Kroeger, Benjamin Robert. “The genetic regulation and subcellular dynamics of secretory and endolysosomal organelles of Drosophila secondary cells.” 2017. Doctoral Dissertation, University of Oxford. Accessed October 21, 2020. http://ora.ox.ac.uk/objects/uuid:dce9ae14-b03d-4fca-8429-de839cc40d6a ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.736126.

MLA Handbook (7th Edition):

Kroeger, Benjamin Robert. “The genetic regulation and subcellular dynamics of secretory and endolysosomal organelles of Drosophila secondary cells.” 2017. Web. 21 Oct 2020.

Vancouver:

Kroeger BR. The genetic regulation and subcellular dynamics of secretory and endolysosomal organelles of Drosophila secondary cells. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2020 Oct 21]. Available from: http://ora.ox.ac.uk/objects/uuid:dce9ae14-b03d-4fca-8429-de839cc40d6a ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.736126.

Council of Science Editors:

Kroeger BR. The genetic regulation and subcellular dynamics of secretory and endolysosomal organelles of Drosophila secondary cells. [Doctoral Dissertation]. University of Oxford; 2017. Available from: http://ora.ox.ac.uk/objects/uuid:dce9ae14-b03d-4fca-8429-de839cc40d6a ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.736126

.