1. Leptin Elongates Hypothalamic Neuronal Cilia via Transcriptional Regulation and Actin Destabilization*
- Author
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Byung-Chul Oh, Ijoo Kwon, Yu Mi Han, Min-Seon Kim, Joon Kim, Hyuk Whan Ko, and Gil Myoung Kang
- Subjects
Leptin ,medicine.medical_specialty ,Phalloidin ,Hypothalamus ,macromolecular substances ,Biology ,Biochemistry ,Cell Line ,chemistry.chemical_compound ,Glycogen Synthase Kinase 3 ,Mice ,Intraflagellar transport ,Internal medicine ,Cell Line, Tumor ,medicine ,Tensin ,Animals ,Humans ,Cilia ,Molecular Biology ,GSK3B ,Neurons ,Leptin Deficiency ,Glycogen Synthase Kinase 3 beta ,Cilium ,digestive, oral, and skin physiology ,PTEN Phosphohydrolase ,Cell Biology ,respiratory system ,Actins ,Cell biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,nervous system ,Gene Expression Regulation ,Neuron ,hormones, hormone substitutes, and hormone antagonists - Abstract
Terminally differentiated neurons have a single, primary cilium. The primary cilia of hypothalamic neurons play a critical role in sensing metabolic signals. We recently showed that mice with leptin deficiency or resistance have shorter cilia in the hypothalamic neurons, and leptin treatment elongates cilia in hypothalamic neurons. Here, we investigated the molecular mechanisms by which leptin controls ciliary length in hypothalamic neurons. In N1 hypothalamic neuronal cells, leptin treatment increased the expression of intraflagellar transport proteins. These effects occurred via phosphatase and tensin homolog/glycogen synthase kinase-3β-mediated inhibition of the transcriptional factor RFX1. Actin filament dynamics were also involved in leptin-promoted ciliary elongation. Both leptin and cytochalasin-D treatment induced F-actin disruption and cilium elongation in hypothalamic neurons that was completely abrogated by co-treatment with the F-actin polymerizer phalloidin. Our findings suggest that leptin elongates hypothalamic neuronal cilia by stimulating the production of intraflagellar transport proteins and destabilizing actin filaments.
- Published
- 2015