ArticleNature neuroscience2014
LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity.
Article in Nature neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 205 citations in OpenAlex.
- Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.Nature communications · 2026Article
- Diffusion Magnetic Resonance Imaging of Cortical Microstructure Differs in Nonmanifest and Manifest Genetic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Parkinson's Disease Patient-Specific Striatum Organoids Show Hallmarks of Increased Inflammation.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of α-synuclein Toxicity in Dopamine Neurons.bioRxiv : the preprint server for biology · 2026Article
- Cell-Free DNA and Mitochondria in Parkinson's Disease.International journal of molecular sciences · 2025Review
- LRRK2 and the fragile synapse: a molecular prelude to Parkinson's disease?The Biochemical journal · 2025Review
- LRRK2 deficiency mitigates amyloid β deposition-mediated pathology in a murine Alzheimer's disease model by reprogramming microglia.Translational psychiatry · 2025Article
- LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons.Molecular psychiatry · 2025Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.bioRxiv : the preprint server for biology · 2025Article
- Alcohol effects on associative and sensorimotor cortico-thalamo-basal ganglia circuits alter decision making and alcohol intake.Alcohol (Fayetteville, N.Y.) · 2025Review
- Striatal cell-type-specific molecular signatures reveal potential therapeutic targets in a model of dystonia.Neurobiology of disease · 2025Article
- Genomics reveals eleven obesity endotypes with distinct biological and phenotypic signatures.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Neuroprotective Role of Cyclic AMP Signaling in Dopaminergic Degeneration Induced by a Parkinson's Disease Toxin, Rotenone.NeuroSci · 2025Article
- Short-term lipopolysaccharide treatment leads to astrocyte activation in LRRK2 G2019S knock-in mice without loss of dopaminergic neurons.BMC neuroscience · 2025Article
- Building an action circuit with nigrostriatal dopaminergic neurons and striatonigral neurons.Handbook of behavioral neuroscience · 2025Article
- The senescent synapse: A look at autophagy, calcium handling, and mitochondrial bioenergetics at the synapse in ageing and Parkinson's disease.Current research in physiology · 2025Review
- Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2bioRxiv : the preprint server for biology · 2024Article
- Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum.Cells · 2024Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is enriched in the striatal projection neurons (SPNs). We found that LRRK2 negatively regulates protein kinase A (PKA) activity in the SPNs during synaptogenesis and in response to dopamine receptor Drd1 activation. LRRK2 interacted with PKA regulatory subunit IIβ (PKARIIβ). A lack of LRRK2 promoted the synaptic translocation of PKA and increased PKA-mediated phosphorylation of actin-disassembling enzyme cofilin and glutamate receptor GluR1, resulting in abnormal synaptogenesis and transmission in the developing SPNs. Furthermore, PKA-dependent phosphorylation of GluR1 was also aberrantly enhanced in the striatum of young and aged Lrrk2(-/-) mice after treatment with a Drd1 agonist. Notably, a Parkinson's disease-related Lrrk2 R1441C missense mutation that impaired the interaction of LRRK2 with PKARIIβ also induced excessive PKA activity in the SPNs. Our findings reveal a previously unknown regulatory role for LRRK2 in PKA signaling and suggest a pathogenic mechanism of SPN dysfunction in Parkinson's disease.
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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.