HTR6

Cilia effects upon perturbation of HTR6

Cilia number / % ciliated:

Unkown

Loss-of-function effect:

Shorter cilia

Overexpression effect:

Longer cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-5.44) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Subcellular localization

basal body, cilia

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)
• Cilia length regulation

Function

Also known as 5-HT6. Regulates length, morphology and function of neuro l primary cilia through ARL13B, influences cilia and axon initial segment. Involved in cognition and Alzheimer鈥檚 disease development (28931427). E ble chemosensory functions in ciliated neurons to sense 5- HT in the immediate milieu (10432491). We found that overexpression of ciliary GPCRs in cortical neurons, especially 5HT6, induced the formation of long (>30 μm) and often forked cilia. These changes were associated with increased levels of intraflagellar transport proteins and accelerated ciliogenesis in neonatal neocortex, the induction of which required Kif3a, an anterograde motor critical for cilia protein trafficking and growth. GPCR overexpression also altered the complement of signaling molecules within the cilia. We found that SSTR3 and type III adenylyl cyclase (ACIII), proteins normally enriched in neuronal cilia, were rarely detected in 5HT6-elongated cilia (23392690). To examine the effect of endogenous 5-HT6 receptor activity on neuronal primary cilia morphology, we used primary cultured striatal neurons to facilitate precise control of drug concentration and ready imaging and measurement of individual primary cilia. Treatment of WT cultured striatal neurons with 1 μM of selective 5-HT6 receptor agonist (WAY-208466) for 24 hours had no effect on primary cilia length, but treatment with the 5-HT6-selective receptor antagonist (SB-399885) for 24 hours significantly reduced the length of primary cilia (28087224).Overexpression of 5HT6 and SSTR3 in mouse neocortical neurons induces abnormal growth of their primary cilia. (23392690)