ArticlePloS one2014
Surfactant secretion in LRRK2 knock-out rats: changes in lamellar body morphology and rate of exocytosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects.NPJ Parkinson's disease · 2022Article
- Autophagy Is Required for Maturation of Surfactant-Containing Lamellar Bodies in the Lung and Swim Bladder.Cell reports · 2020Article
- The Role of Human LRRK2 in Methylmercury-Induced Inhibition of Microvesicle Formation of Cephalic Neurons in Caenorhabditis elegans.Neurotoxicity research · 2020Article
- Analysis of purine receptor expression and functionality in alveolar epithelial cells.Purinergic signalling · 2020Article
- Progress inFrontiers in neuroscience · 2020Review
- Glial phagocytic clearance in Parkinson's disease.Molecular neurodegeneration · 2019Review
- Physiological and pathological functions of LRRK2: implications from substrate proteins.Neuronal signaling · 2018Review
- Long-term expansion of alveolar stem cells derived from human iPS cells in organoids.Nature methods · 2017Article
- Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation.Scientific reports · 2016Article
- Two-Pore Channels and Parkinson's Disease: Where's the Link?Messenger (Los Angeles, Calif. : Print) · 2016Article
- SNAREs in the maturation and function of LROs.Bioarchitecture · 2016Review
- Leucine-rich repeat kinase 2 positively regulates inflammation and down-regulates NF-κB p50 signaling in cultured microglia cells.Journal of neuroinflammation · 2015Article
- The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease.Neuroscience · 2015Review
- Cellular processes associated with LRRK2 function and dysfunction.The FEBS journal · 2015Review
- LRRK2 dephosphorylation increases its ubiquitination.The Biochemical journal · 2015Article
- Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice.Neurobiology of disease · 2015Article
- Actin depolymerisation and crosslinking join forces with myosin II to contract actin coats on fused secretory vesicles.Journal of cell science · 2015Article
- Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on α-synuclein.Neuron · 2015Article
- Synaptotagmin-7 links fusion-activated Ca²⁺ entry and fusion pore dilation.Journal of cell science · 2014Article
- Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy.Human molecular genetics · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is known to play a role in the pathogenesis of various diseases including Parkinson disease, morbus Crohn, leprosy and cancer. LRRK2 is suggested to be involved in a number of cell biological processes such as vesicular trafficking, transcription, autophagy and lysosomal pathways. Recent histological studies of lungs of LRRK2 knock-out (LRRK2 -/-) mice revealed significantly enlarged lamellar bodies (LBs) in alveolar type II (ATII) epithelial cells. LBs are large, lysosome-related storage organelles for pulmonary surfactant, which is released into the alveolar lumen upon LB exocytosis. In this study we used high-resolution, subcellular live-cell imaging assays to investigate whether similar morphological changes can be observed in primary ATII cells from LRRK2 -/- rats and whether such changes result in altered LB exocytosis. Similarly to the report in mice, ATII cells from LRRK2 -/- rats contained significantly enlarged LBs resulting in a >50% increase in LB volume. Stimulation of ATII cells with ATP elicited LB exocytosis in a significantly increased proportion of cells from LRRK2 -/- animals. LRRK2 -/- cells also displayed increased intracellular Ca(2+) release upon ATP treatment and significant triggering of LB exocytosis. These findings are in line with the strong Ca(2+)-dependence of LB fusion activity and suggest that LRRK2 -/- affects exocytic response in ATII cells via modulating intracellular Ca(2+) signaling. Post-fusion regulation of surfactant secretion was unaltered. Actin coating of fused vesicles and subsequent vesicle compression to promote surfactant expulsion were comparable in cells from LRRK2 -/- and wt animals. Surprisingly, surfactant (phospholipid) release from LRRK2 -/- cells was reduced following stimulation of LB exocytosis possibly due to impaired LB maturation and surfactant loading of LBs. In summary our results suggest that LRRK2 -/- affects LB size, modulates intracellular Ca(2+) signaling and promotes LB exocytosis upon stimulation of ATII cells with ATP.
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