The role of small GTPases in regulating sleep in Drosophila melanogaster
<p>Sleep is highly conserved across the animal kingdom, yet why and how we sleep remains largely unknown. Uncovering the molecular pathway underlying homeostatic sleep regulation is integral to understanding the origin and function of sleep, as well as for the development of spatiotemporally p...
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| 格式: | Thesis |
| 语言: | English |
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2021
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| _version_ | 1826316414802198528 |
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| author | Hartmann, C |
| author2 | Miesenboeck, G |
| author_facet | Miesenboeck, G Hartmann, C |
| author_sort | Hartmann, C |
| collection | OXFORD |
| description | <p>Sleep is highly conserved across the animal kingdom, yet why and how we sleep remains largely unknown. Uncovering the molecular pathway underlying homeostatic sleep regulation is integral to understanding the origin and function of sleep, as well as for the development of spatiotemporally precise medication to treat sleep disorders. </p>
<p>In the model organism, <em>Drosophila melanogaster</em>, neurons that project to the dorsal fan shaped body (dFB neurons) form a critical part of the sleep homeostat. By switching between their electrically-silent (OFF) state and electrically-active (ON) state, dFB neurons respond to increasing sleep pressure by inducing sleep. Previous work identified that mutating <em>crossveinless-c (cv-c)</em>, a gene encoding a Rho-GTPase activating protein (Rho GAP), locks dFB neurons in the OFF state and results in an insomniac phenotype. Since GAPs are essential for the hydrolysis of small GTPases from their active (GTP-bound) to their inactive (GDP-bound) state, this thesis aimed to uncover the role of small GTPases in sleep regulation. A combination of genetic interaction, behaviour and imaging experiments were used. </p>
<p>The work presented here demonstrates that active Rho1 is upregulated in dFB neurons of cv-c mutants, and that manipulating Rho1 in dFB neurons of cv-c mutants rescues the insomniac phenotype. In addition, knocking down Rho1 in cv-c mutants restores dFB neuron excitability. This suggests that Rho1 is an important part of the molecular pathway underlying sleep regulation. However, the nature of how Rho1 regulates dFB membrane excitability, and to what extent its interacting partner Rac1 is involved, remains unclear. The findings of this thesis suggest a vexingly complex role of small GTPases in regulating sleep and highlights the importance of finely-tuned regulation of these signalling proteins. </p>
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| first_indexed | 2024-03-06T21:13:26Z |
| format | Thesis |
| id | oxford-uuid:3ef3aab3-b445-4a6d-b853-62845a1d7cde |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:44:44Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:3ef3aab3-b445-4a6d-b853-62845a1d7cde2024-12-07T16:16:08ZThe role of small GTPases in regulating sleep in Drosophila melanogasterThesishttp://purl.org/coar/resource_type/c_bdccuuid:3ef3aab3-b445-4a6d-b853-62845a1d7cdeNeurobiologySleepDrosophila melanogasterSmall GTPasesEnglishHyrax Deposit2021Hartmann, CMiesenboeck, G<p>Sleep is highly conserved across the animal kingdom, yet why and how we sleep remains largely unknown. Uncovering the molecular pathway underlying homeostatic sleep regulation is integral to understanding the origin and function of sleep, as well as for the development of spatiotemporally precise medication to treat sleep disorders. </p> <p>In the model organism, <em>Drosophila melanogaster</em>, neurons that project to the dorsal fan shaped body (dFB neurons) form a critical part of the sleep homeostat. By switching between their electrically-silent (OFF) state and electrically-active (ON) state, dFB neurons respond to increasing sleep pressure by inducing sleep. Previous work identified that mutating <em>crossveinless-c (cv-c)</em>, a gene encoding a Rho-GTPase activating protein (Rho GAP), locks dFB neurons in the OFF state and results in an insomniac phenotype. Since GAPs are essential for the hydrolysis of small GTPases from their active (GTP-bound) to their inactive (GDP-bound) state, this thesis aimed to uncover the role of small GTPases in sleep regulation. A combination of genetic interaction, behaviour and imaging experiments were used. </p> <p>The work presented here demonstrates that active Rho1 is upregulated in dFB neurons of cv-c mutants, and that manipulating Rho1 in dFB neurons of cv-c mutants rescues the insomniac phenotype. In addition, knocking down Rho1 in cv-c mutants restores dFB neuron excitability. This suggests that Rho1 is an important part of the molecular pathway underlying sleep regulation. However, the nature of how Rho1 regulates dFB membrane excitability, and to what extent its interacting partner Rac1 is involved, remains unclear. The findings of this thesis suggest a vexingly complex role of small GTPases in regulating sleep and highlights the importance of finely-tuned regulation of these signalling proteins. </p> |
| spellingShingle | Neurobiology Sleep Drosophila melanogaster Small GTPases Hartmann, C The role of small GTPases in regulating sleep in Drosophila melanogaster |
| title | The role of small GTPases in regulating sleep in Drosophila melanogaster |
| title_full | The role of small GTPases in regulating sleep in Drosophila melanogaster |
| title_fullStr | The role of small GTPases in regulating sleep in Drosophila melanogaster |
| title_full_unstemmed | The role of small GTPases in regulating sleep in Drosophila melanogaster |
| title_short | The role of small GTPases in regulating sleep in Drosophila melanogaster |
| title_sort | role of small gtpases in regulating sleep in drosophila melanogaster |
| topic | Neurobiology Sleep Drosophila melanogaster Small GTPases |
| work_keys_str_mv | AT hartmannc theroleofsmallgtpasesinregulatingsleepindrosophilamelanogaster AT hartmannc roleofsmallgtpasesinregulatingsleepindrosophilamelanogaster |