The microtubule-associated protein Tau suppresses the axonal distribution of PDF neuropeptide and mitochondria in circadian clock neurons
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissionsoup.com..
Disrupted circadian rhythms are a prominent feature of multiple neurodegenerative diseases. Yet mechanisms linking Tau to rhythmic behavior remain unclear. Here, we find that expression of a phosphomimetic human Tau mutant (TauE14) in Drosophila circadian pacemaker neurons disrupts free-running rhythmicity. While cell number and oscillations of the core clock protein PERIOD are unaffected in the small LNv (sLNv) neurons important for free running rhythms, we observe a near complete loss of the major LNv neuropeptide pigment dispersing factor (PDF) in the dorsal axonal projections of the sLNvs. This was accompanied by a ~50% reduction in the area of the dorsal terminals and a modest decrease in cell body PDF levels. Expression of wild-type Tau also reduced axonal PDF levels but to a lesser extent than TauE14. TauE14 also induces a complete loss of mitochondria from these sLNv projections. However, mitochondria were increased in sLNv cell bodies in TauE14 flies. These results suggest that TauE14 disrupts axonal transport of neuropeptides and mitochondria in circadian pacemaker neurons, providing a mechanism by which Tau can disrupt circadian behavior prior to cell loss.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Human molecular genetics - 31(2022), 7 vom: 31. März, Seite 1141-1150 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Melanie Y [VerfasserIn] |
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| Links: |
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| Themen: |
Drosophila Proteins |
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| Anmerkungen: |
Date Completed 06.04.2022 Date Revised 09.11.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/hmg/ddab303 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM332886484 |
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| 100 | 1 | |a Zhang, Melanie Y |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The microtubule-associated protein Tau suppresses the axonal distribution of PDF neuropeptide and mitochondria in circadian clock neurons |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a Disrupted circadian rhythms are a prominent feature of multiple neurodegenerative diseases. Yet mechanisms linking Tau to rhythmic behavior remain unclear. Here, we find that expression of a phosphomimetic human Tau mutant (TauE14) in Drosophila circadian pacemaker neurons disrupts free-running rhythmicity. While cell number and oscillations of the core clock protein PERIOD are unaffected in the small LNv (sLNv) neurons important for free running rhythms, we observe a near complete loss of the major LNv neuropeptide pigment dispersing factor (PDF) in the dorsal axonal projections of the sLNvs. This was accompanied by a ~50% reduction in the area of the dorsal terminals and a modest decrease in cell body PDF levels. Expression of wild-type Tau also reduced axonal PDF levels but to a lesser extent than TauE14. TauE14 also induces a complete loss of mitochondria from these sLNv projections. However, mitochondria were increased in sLNv cell bodies in TauE14 flies. These results suggest that TauE14 disrupts axonal transport of neuropeptides and mitochondria in circadian pacemaker neurons, providing a mechanism by which Tau can disrupt circadian behavior prior to cell loss | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Drosophila Proteins |2 NLM | |
| 650 | 7 | |a Neuropeptides |2 NLM | |
| 650 | 7 | |a pdf protein, Drosophila |2 NLM | |
| 700 | 1 | |a Lear, Bridget C |e verfasserin |4 aut | |
| 700 | 1 | |a Allada, Ravi |e verfasserin |4 aut | |
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