ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Selective expression of a dominant-negative type Iα PKA regulatory subunit in striatal medium spiny neurons impairs gene expression and leads to reduced feeding and locomotor activity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- A small molecule reduces both parkinsonism and l-dopa-induced dyskinesia in animal models of Parkinson's disease.Science translational medicine · 2026Article
- E3 ubiquitin ligase CHIP facilitates cAMP and cGMP signalling cross-talk by polyubiquitinating PDE9A.The EMBO journal · 2025Article
- Neuronal ER-plasma membrane junctions couple excitation to CaNature communications · 2023Article
- RIIβ-PKA in GABAergic Neurons of Dorsal Median Hypothalamus Governs White Adipose Browning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The PRKAR1B p.R115K Variant is Associated with Lipoprotein Profile in African American Youth with Metabolic Challenges.Journal of the Endocrine Society · 2021Article
- Loss of habenular Prkar2a reduces hedonic eating and increases exercise motivation.JCI insight · 2020Article
- PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies.The Journal of endocrinology · 2020Review
- Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system.Nature communications · 2019Article
- cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits.The Journal of biological chemistry · 2019Article
- Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement.Nature reviews. Endocrinology · 2018Review
- Altered phosphorylation, electrophysiology, and behavior on attenuation of PDE4B action in hippocampus.BMC neuroscience · 2017Article
- Locomotion Behavior Is Affected by the GαGenetics · 2017Article
- Article
- Effects of a novel phosphodiesterase 10A inhibitor in non-human primates: A therapeutic approach for schizophrenia with improved side effect profile.Neuropharmacology · 2016Article
- Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2(-/y) ) Mice by Rolipram.Frontiers in cellular neuroscience · 2016Article
- Hypothalamic PKA regulates leptin sensitivity and adiposity.Nature communications · 2015Article
- Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Striatal medium spiny neurons (MSNs) mediate many of the physiological effects of dopamine, including the regulation of feeding and motor behaviors. Dopaminergic inputs from the midbrain modulate MSN excitability through pathways that involve cAMP and protein kinase A (PKA), but the physiological role of specific PKA isoforms in MSN neurons remains poorly understood. One of the major PKA regulatory (R) subunit isoforms expressed in MSNs is RIIβ, which localizes the PKA holoenzyme primarily to dendrites by interaction with AKAP5 and other scaffolding proteins. However, RI (RIα and RIβ) subunits are also expressed in MSNs and the RI holoenzyme has a weaker affinity for most scaffolding proteins and tends to localize in the cell body. We generated mice with selective expression of a dominant-negative RI subunit (RIαB) in striatal MSNs and show that this dominant-negative RIαB localizes to the cytoplasm and specifically inhibits type I PKA activity in the striatum. These mice are normal at birth; however, soon after weaning they exhibit growth retardation and the adult mice are hypophagic, lean, and resistant to high-fat diet-induced hyperphagia and obesity. The RIαB-expressing mice also exhibit decreased locomotor activity and decreased dopamine-regulated CREB phosphorylation and c-fos gene expression in the striatum. Our results demonstrate a critical role for cytoplasmic RI-PKA holoenzyme in gene regulation and the overall physiological function of MSNs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.