INPP5E controls ciliary localization of phospholipids and the odor response in olfactory sensory neurons
© 2021. Published by The Company of Biologists Ltd..
The lipid composition of the primary cilia membrane is emerging as a critical regulator of cilia formation, maintenance and function. Here, we show that conditional deletion of the phosphoinositide 5'-phosphatase gene Inpp5e, mutation of which is causative of Joubert syndrome, in terminally developed mouse olfactory sensory neurons (OSNs), leads to a dramatic remodeling of ciliary phospholipids that is accompanied by marked elongation of cilia. Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2], which is normally restricted to the proximal segment redistributed to the entire length of cilia in Inpp5e knockout mice with a reduction in phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2] and elevation of phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] in the dendritic knob. The redistribution of phosphoinositides impaired odor adaptation, resulting in less efficient recovery and altered inactivation kinetics of the odor-evoked electrical response and the odor-induced elevation of cytoplasmic Ca2+. Gene replacement of Inpp5e through adenoviral expression restored the ciliary localization of PI(4,5)P2 and odor response kinetics in OSNs. Our findings support the role of phosphoinositides as a modulator of the odor response and in ciliary biology of native multi-ciliated OSNs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:135 |
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| Enthalten in: |
Journal of cell science - 135(2022), 5 vom: 01. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ukhanov, Kirill [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.06.2021 Date Revised 19.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1242/jcs.258364 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a INPP5E controls ciliary localization of phospholipids and the odor response in olfactory sensory neurons |
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| 500 | |a Date Revised 19.05.2023 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. Published by The Company of Biologists Ltd. | ||
| 520 | |a The lipid composition of the primary cilia membrane is emerging as a critical regulator of cilia formation, maintenance and function. Here, we show that conditional deletion of the phosphoinositide 5'-phosphatase gene Inpp5e, mutation of which is causative of Joubert syndrome, in terminally developed mouse olfactory sensory neurons (OSNs), leads to a dramatic remodeling of ciliary phospholipids that is accompanied by marked elongation of cilia. Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2], which is normally restricted to the proximal segment redistributed to the entire length of cilia in Inpp5e knockout mice with a reduction in phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2] and elevation of phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] in the dendritic knob. The redistribution of phosphoinositides impaired odor adaptation, resulting in less efficient recovery and altered inactivation kinetics of the odor-evoked electrical response and the odor-induced elevation of cytoplasmic Ca2+. Gene replacement of Inpp5e through adenoviral expression restored the ciliary localization of PI(4,5)P2 and odor response kinetics in OSNs. Our findings support the role of phosphoinositides as a modulator of the odor response and in ciliary biology of native multi-ciliated OSNs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a INPP5E | |
| 650 | 4 | |a Mouse | |
| 650 | 4 | |a Odor response | |
| 650 | 4 | |a Olfactory cilia | |
| 650 | 4 | |a Phospholipids | |
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| 700 | 1 | |a Uytingco, Cedric |e verfasserin |4 aut | |
| 700 | 1 | |a Green, Warren |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lian |e verfasserin |4 aut | |
| 700 | 1 | |a Schurmans, Stephane |e verfasserin |4 aut | |
| 700 | 1 | |a Martens, Jeffrey R |e verfasserin |4 aut | |
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