Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons.
Leptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP)/Neuropeptide Y (NPY)/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3812230?pdf=render |
| _version_ | 1818421650569297920 |
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| author | Sangdeuk Ha Scott Baver Lihong Huo Adriana Gata Joyce Hairston Nicholas Huntoon Wenjing Li Thompson Zhang Elizabeth J Benecchi Maria Ericsson Shane T Hentges Christian Bjørbæk |
| author_facet | Sangdeuk Ha Scott Baver Lihong Huo Adriana Gata Joyce Hairston Nicholas Huntoon Wenjing Li Thompson Zhang Elizabeth J Benecchi Maria Ericsson Shane T Hentges Christian Bjørbæk |
| author_sort | Sangdeuk Ha |
| collection | DOAJ |
| description | Leptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP)/Neuropeptide Y (NPY)/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin receptor (LepRb). Despite progress in the understanding of LepRb signaling and function, the sub-cellular localization of LepRb in target neurons has not been determined, primarily due to lack of sensitive anti-LepRb antibodies. Here we applied light microscopy (LM), confocal-laser scanning microscopy (CLSM), and electron microscopy (EM) to investigate LepRb localization and signaling in mice expressing a HA-tagged LepRb selectively in POMC or AgRP/NPY/GABA neurons. We report that LepRb receptors exhibit a somato-dendritic expression pattern. We further show that LepRb activates STAT3 phosphorylation in neuronal fibers within several hypothalamic and hindbrain nuclei of wild-type mice and rats, and specifically in dendrites of arcuate POMC and AgRP/NPY/GABA neurons of Leprb (+/+) mice and in Leprb (db/db) mice expressing HA-LepRb in a neuron specific manner. We did not find evidence of LepRb localization or STAT3-signaling in axon-fibers or nerve-terminals of POMC and AgRP/NPY/GABA neurons. Three-dimensional serial EM-reconstruction of dendritic segments from POMC and AgRP/NPY/GABA neurons indicates a high density of shaft synapses. In addition, we found that the leptin activates STAT3 signaling in proximity to synapses on POMC and AgRP/NPY/GABA dendritic shafts. Taken together, these data suggest that the signaling-form of the leptin receptor exhibits a somato-dendritic expression pattern in POMC and AgRP/NPY/GABA neurons. Dendritic LepRb signaling may therefore play an important role in leptin's central effects on energy balance, possibly through modulation of synaptic activity via post-synaptic mechanisms. |
| first_indexed | 2024-12-14T13:13:44Z |
| format | Article |
| id | doaj.art-0371305d335f4e259d2bb1fd50f9bfa2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T13:13:44Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0371305d335f4e259d2bb1fd50f9bfa22022-12-21T23:00:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7762210.1371/journal.pone.0077622Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons.Sangdeuk HaScott BaverLihong HuoAdriana GataJoyce HairstonNicholas HuntoonWenjing LiThompson ZhangElizabeth J BenecchiMaria EricssonShane T HentgesChristian BjørbækLeptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP)/Neuropeptide Y (NPY)/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin receptor (LepRb). Despite progress in the understanding of LepRb signaling and function, the sub-cellular localization of LepRb in target neurons has not been determined, primarily due to lack of sensitive anti-LepRb antibodies. Here we applied light microscopy (LM), confocal-laser scanning microscopy (CLSM), and electron microscopy (EM) to investigate LepRb localization and signaling in mice expressing a HA-tagged LepRb selectively in POMC or AgRP/NPY/GABA neurons. We report that LepRb receptors exhibit a somato-dendritic expression pattern. We further show that LepRb activates STAT3 phosphorylation in neuronal fibers within several hypothalamic and hindbrain nuclei of wild-type mice and rats, and specifically in dendrites of arcuate POMC and AgRP/NPY/GABA neurons of Leprb (+/+) mice and in Leprb (db/db) mice expressing HA-LepRb in a neuron specific manner. We did not find evidence of LepRb localization or STAT3-signaling in axon-fibers or nerve-terminals of POMC and AgRP/NPY/GABA neurons. Three-dimensional serial EM-reconstruction of dendritic segments from POMC and AgRP/NPY/GABA neurons indicates a high density of shaft synapses. In addition, we found that the leptin activates STAT3 signaling in proximity to synapses on POMC and AgRP/NPY/GABA dendritic shafts. Taken together, these data suggest that the signaling-form of the leptin receptor exhibits a somato-dendritic expression pattern in POMC and AgRP/NPY/GABA neurons. Dendritic LepRb signaling may therefore play an important role in leptin's central effects on energy balance, possibly through modulation of synaptic activity via post-synaptic mechanisms.http://europepmc.org/articles/PMC3812230?pdf=render |
| spellingShingle | Sangdeuk Ha Scott Baver Lihong Huo Adriana Gata Joyce Hairston Nicholas Huntoon Wenjing Li Thompson Zhang Elizabeth J Benecchi Maria Ericsson Shane T Hentges Christian Bjørbæk Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons. PLoS ONE |
| title | Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons. |
| title_full | Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons. |
| title_fullStr | Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons. |
| title_full_unstemmed | Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons. |
| title_short | Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons. |
| title_sort | somato dendritic localization and signaling by leptin receptors in hypothalamic pomc and agrp neurons |
| url | http://europepmc.org/articles/PMC3812230?pdf=render |
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