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Updated: Nov 14, 2025

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
Published on: September 18, 2013
NAPE-specific phospholipase D regulates LRRK2 association with neuronal membranes
Francesca Palese1, Silvia Pontis2, Natalia Realini2
1Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; Departments of Anatomy and Neurobiology, Pharmacology and Biological Chemistry, University of California, Irvine, CA, United States.
Abstract:
N-acylphosphatidylethanolamines (NAPEs) are glycerophospholipid precursors for bioactive lipid amides and potential regulators of membrane function. They are hydrolyzed by NAPE-specific phospholipase D (NAPE-PLD) and have been implicated in neurodegenerative disorders such as Parkinson's disease. Here, we used siRNA-mediated silencing of NAPE-PLD in human SH-SY5Y cells and NAPE-PLD-/- mice to determine whether NAPEs influence the membrane association of LRRK2, a multifunctional protein kinase that is frequently mutated in persons with sporadic Parkinson's disease. NAPE-PLD deletion caused a significant accumulation of non-metabolized NAPEs, which was accompanied by a shift of LRRK2 from membrane to cytosol and a reduction in total LRRK2 content. Conversely, exposure of intact SH-SY5Y cells to bacterial PLD lowered NAPE levels and enhanced LRRK2 association with membranes. The results suggest that NAPE-PLD activity may contribute to the control of LRRK2 localization by regulating membrane NAPE levels.
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