The Primary Cilia are Associated with the Axon Initial Segment in Neurons
Abstract The primary cilia serve as pivotal mediators of environmental signals and play crucial roles in neuronal responses. Disruption of ciliary function has been implicated in neuronal circuit disorders and aberrant neuronal excitability. However, the precise mechanisms remain elusive. To study t...
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202407405 |
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| author | Han Wang Yu Li Xin Li Zehui Sun Fengdan Yu Abolghasem Pashang Don Kulasiri Hung Wing Li Huan Chen Hongwei Hou Yan Zhang |
| author_facet | Han Wang Yu Li Xin Li Zehui Sun Fengdan Yu Abolghasem Pashang Don Kulasiri Hung Wing Li Huan Chen Hongwei Hou Yan Zhang |
| author_sort | Han Wang |
| collection | DOAJ |
| description | Abstract The primary cilia serve as pivotal mediators of environmental signals and play crucial roles in neuronal responses. Disruption of ciliary function has been implicated in neuronal circuit disorders and aberrant neuronal excitability. However, the precise mechanisms remain elusive. To study the link between the primary cilia and neuronal excitability, manipulation of somatostatin receptor 3 (SSTR3) is investigated, as an example of how alterations in ciliary signaling may affect neuronal activity. It is found that aberrant SSTR3 expression perturbed not only ciliary morphology but also disrupted ciliary signaling cascades. Genetic deletion of SSTR3 resulted in perturbed spatial memory and synaptic plasticity. The axon initial segment (AIS) is a specialized region in the axon where action potentials are initiated. Interestingly, loss of ciliary SSTR3 led to decrease of Akt‐dependent cyclic AMP‐response element binding protein (CREB)‐mediated transcription at the AIS, specifically downregulating AIS master organizer adaptor protein ankyrin G (AnkG) expression. In addition, alterations of other ciliary proteins serotonin 6 receptor (5‐HT6R)and intraflagellar transport protein 88 (IFT88) also induced length changes of the AIS. The findings elucidate a specific interaction between the primary cilia and AIS, providing insight into the impact of the primary cilia on neuronal excitability and circuit integrity. |
| format | Article |
| id | doaj-art-9a22a16ebd684cc6b297dd4bce51910e |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-9a22a16ebd684cc6b297dd4bce51910e2025-08-20T03:24:44ZengWileyAdvanced Science2198-38442025-03-01129n/an/a10.1002/advs.202407405The Primary Cilia are Associated with the Axon Initial Segment in NeuronsHan Wang0Yu Li1Xin Li2Zehui Sun3Fengdan Yu4Abolghasem Pashang5Don Kulasiri6Hung Wing Li7Huan Chen8Hongwei Hou9Yan Zhang10State Key Laboratory of Membrane Biology School of Life Sciences Peking University Beijing 100871 ChinaState Key Laboratory of Membrane Biology School of Life Sciences Peking University Beijing 100871 ChinaBeijing Life Science Academy Beijing 102200 ChinaState Key Laboratory of Membrane Biology School of Life Sciences Peking University Beijing 100871 ChinaState Key Laboratory of Membrane Biology School of Life Sciences Peking University Beijing 100871 ChinaCentre for Advanced Computational Solutions (C‐fACS) AGLS faculty Lincoln University Canterbury 7647 New ZealandCentre for Advanced Computational Solutions (C‐fACS) AGLS faculty Lincoln University Canterbury 7647 New ZealandDepartment of Chemistry The Chinese University of Hong Kong Hong Kong 999077 ChinaBeijing Life Science Academy Beijing 102200 ChinaBeijing Life Science Academy Beijing 102200 ChinaState Key Laboratory of Membrane Biology School of Life Sciences Peking University Beijing 100871 ChinaAbstract The primary cilia serve as pivotal mediators of environmental signals and play crucial roles in neuronal responses. Disruption of ciliary function has been implicated in neuronal circuit disorders and aberrant neuronal excitability. However, the precise mechanisms remain elusive. To study the link between the primary cilia and neuronal excitability, manipulation of somatostatin receptor 3 (SSTR3) is investigated, as an example of how alterations in ciliary signaling may affect neuronal activity. It is found that aberrant SSTR3 expression perturbed not only ciliary morphology but also disrupted ciliary signaling cascades. Genetic deletion of SSTR3 resulted in perturbed spatial memory and synaptic plasticity. The axon initial segment (AIS) is a specialized region in the axon where action potentials are initiated. Interestingly, loss of ciliary SSTR3 led to decrease of Akt‐dependent cyclic AMP‐response element binding protein (CREB)‐mediated transcription at the AIS, specifically downregulating AIS master organizer adaptor protein ankyrin G (AnkG) expression. In addition, alterations of other ciliary proteins serotonin 6 receptor (5‐HT6R)and intraflagellar transport protein 88 (IFT88) also induced length changes of the AIS. The findings elucidate a specific interaction between the primary cilia and AIS, providing insight into the impact of the primary cilia on neuronal excitability and circuit integrity.https://doi.org/10.1002/advs.2024074055‐HT6Raxon initial segmentciliary GPCRprimary ciliaSSTR3 |
| spellingShingle | Han Wang Yu Li Xin Li Zehui Sun Fengdan Yu Abolghasem Pashang Don Kulasiri Hung Wing Li Huan Chen Hongwei Hou Yan Zhang The Primary Cilia are Associated with the Axon Initial Segment in Neurons Advanced Science 5‐HT6R axon initial segment ciliary GPCR primary cilia SSTR3 |
| title | The Primary Cilia are Associated with the Axon Initial Segment in Neurons |
| title_full | The Primary Cilia are Associated with the Axon Initial Segment in Neurons |
| title_fullStr | The Primary Cilia are Associated with the Axon Initial Segment in Neurons |
| title_full_unstemmed | The Primary Cilia are Associated with the Axon Initial Segment in Neurons |
| title_short | The Primary Cilia are Associated with the Axon Initial Segment in Neurons |
| title_sort | primary cilia are associated with the axon initial segment in neurons |
| topic | 5‐HT6R axon initial segment ciliary GPCR primary cilia SSTR3 |
| url | https://doi.org/10.1002/advs.202407405 |
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