title: Leptin Elongates Hypothalamic Neuronal Cilia via Transcriptional Regulation and Actin Destabilization.
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.
authors.affiliation: Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Gil Myoung
authors.initials: GM
authors.lastname: Kang
authors.affiliation: Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Han
authors.affiliation: College of Pharmacy, Dongguk University, Goyangsi, Gyeonggido 410-773, Korea.
authors.forename: Hyuk Whan
authors.initials: HW
authors.lastname: Ko
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-338, Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Oh
authors.affiliation: Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Ijoo
authors.initials: I
authors.lastname: Kwon
authors.affiliation: Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine, Seoul 138-736, Korea; Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea. Electronic address: mskim@amc.seoul.kr.
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism
chemical_list: D000199:Actins; D020738:Leptin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase
keywords: F-actin; cilia; glycogen synthase kinase-3β; hypothalamus; leptin; neuron; phosphatase and tensin homolog (PTEN)