Regulation and reproductive functions of membrane-bound vesicles secreted by the Drosophila male accessory gland
<p>Membrane-bound vesicle secretion provides a novel intercellular communication mechanism, whose roles and regulation remain poorly characterised, particularly <em>in vivo</em>. I have identified two classes of lipid-containing, vesicle-like structures secreted into seminal fluid...
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| Format: | Thesis |
| Language: | English |
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2014
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| _version_ | 1826276592082485248 |
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| author | Corrigan, L |
| author2 | Wilson, C |
| author_facet | Wilson, C Corrigan, L |
| author_sort | Corrigan, L |
| collection | OXFORD |
| description | <p>Membrane-bound vesicle secretion provides a novel intercellular communication mechanism, whose roles and regulation remain poorly characterised, particularly <em>in vivo</em>. I have identified two classes of lipid-containing, vesicle-like structures secreted into seminal fluid by epithelial cells of the <em>Drosophila</em> male accessory gland (AG). Exosomes, one class of membrane-bound vesicle formed inside late endosomal multivesicular bodies, are specifically secreted by secondary cells (SCs). The unusual cell biology of SCs allowed me to develop a powerful new high resolution <em>in vivo</em> system to characterise the mechanisms underlying intracellular membrane trafficking events underlying exosome biogenesis using real-time live imaging. I characterise how specific ESCRTs (endosomal sorting complexes required for transport) control SC exosome biogenesis, and identify a novel role for BMP signalling in regulating endolysosomal trafficking events necessary for exosome secretion. I also identify roles for epidermal growth factor receptor (EGFR) and phosphatidylinositide 3-kinase (PI3K) signalling in exosome biogenesis. Importantly, SC exosomes are transferred to females during mating. Here, they fuse with sperm, mirroring <em>in vitro</em> interactions between human prostate exosomes and sperm, and interact with the female reproductive tract epithelium. Blocking SC exosome production specifically suppresses post-mating effects on female receptivity to remating, demonstrating that exosomes have an important reproductive signalling function <em>in vivo</em>, directly or indirectly reprogramming female cells. Finally, I show that main cells, the major epithelial AG cell type, shed lipid-containing microvesicle-like structures from their apical surface. Remarkably, these vesicles carry the seminal peptide, sex peptide, into females during mating and also contribute to the anterior mating plug. In summary, my data reveal previously unsuspected roles for exosomes and microvesicles in <em>Drosophila</em> reproduction that may be evolutionarily conserved. Since these vesicles mediate physiological processes previously thought to involve soluble peptides, my work suggests that current models explaining male reprogramming of female behaviours in flies and higher organisms need substantial revision.</p> |
| first_indexed | 2024-03-06T23:16:16Z |
| format | Thesis |
| id | oxford-uuid:673d46a5-ba88-42d2-9361-51f04d61e01b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:16:16Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:673d46a5-ba88-42d2-9361-51f04d61e01b2022-03-26T18:36:55ZRegulation and reproductive functions of membrane-bound vesicles secreted by the Drosophila male accessory glandThesishttp://purl.org/coar/resource_type/c_db06uuid:673d46a5-ba88-42d2-9361-51f04d61e01bCell Biology (see also Plant sciences)Genetics (life sciences)EnglishOxford University Research Archive - Valet2014Corrigan, LWilson, C<p>Membrane-bound vesicle secretion provides a novel intercellular communication mechanism, whose roles and regulation remain poorly characterised, particularly <em>in vivo</em>. I have identified two classes of lipid-containing, vesicle-like structures secreted into seminal fluid by epithelial cells of the <em>Drosophila</em> male accessory gland (AG). Exosomes, one class of membrane-bound vesicle formed inside late endosomal multivesicular bodies, are specifically secreted by secondary cells (SCs). The unusual cell biology of SCs allowed me to develop a powerful new high resolution <em>in vivo</em> system to characterise the mechanisms underlying intracellular membrane trafficking events underlying exosome biogenesis using real-time live imaging. I characterise how specific ESCRTs (endosomal sorting complexes required for transport) control SC exosome biogenesis, and identify a novel role for BMP signalling in regulating endolysosomal trafficking events necessary for exosome secretion. I also identify roles for epidermal growth factor receptor (EGFR) and phosphatidylinositide 3-kinase (PI3K) signalling in exosome biogenesis. Importantly, SC exosomes are transferred to females during mating. Here, they fuse with sperm, mirroring <em>in vitro</em> interactions between human prostate exosomes and sperm, and interact with the female reproductive tract epithelium. Blocking SC exosome production specifically suppresses post-mating effects on female receptivity to remating, demonstrating that exosomes have an important reproductive signalling function <em>in vivo</em>, directly or indirectly reprogramming female cells. Finally, I show that main cells, the major epithelial AG cell type, shed lipid-containing microvesicle-like structures from their apical surface. Remarkably, these vesicles carry the seminal peptide, sex peptide, into females during mating and also contribute to the anterior mating plug. In summary, my data reveal previously unsuspected roles for exosomes and microvesicles in <em>Drosophila</em> reproduction that may be evolutionarily conserved. Since these vesicles mediate physiological processes previously thought to involve soluble peptides, my work suggests that current models explaining male reprogramming of female behaviours in flies and higher organisms need substantial revision.</p> |
| spellingShingle | Cell Biology (see also Plant sciences) Genetics (life sciences) Corrigan, L Regulation and reproductive functions of membrane-bound vesicles secreted by the Drosophila male accessory gland |
| title | Regulation and reproductive functions of membrane-bound vesicles secreted by the Drosophila male accessory gland |
| title_full | Regulation and reproductive functions of membrane-bound vesicles secreted by the Drosophila male accessory gland |
| title_fullStr | Regulation and reproductive functions of membrane-bound vesicles secreted by the Drosophila male accessory gland |
| title_full_unstemmed | Regulation and reproductive functions of membrane-bound vesicles secreted by the Drosophila male accessory gland |
| title_short | Regulation and reproductive functions of membrane-bound vesicles secreted by the Drosophila male accessory gland |
| title_sort | regulation and reproductive functions of membrane bound vesicles secreted by the drosophila male accessory gland |
| topic | Cell Biology (see also Plant sciences) Genetics (life sciences) |
| work_keys_str_mv | AT corriganl regulationandreproductivefunctionsofmembraneboundvesiclessecretedbythedrosophilamaleaccessorygland |