NAPE-specific phospholipase D regulates LRRK2 association with neuronal membranes

Adv Pharmacol. 2021;90:217-238. doi: 10.1016/bs.apha.2020.09.003. Epub 2020 Oct 6.ABSTRACTN-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.PMID:33706934 | DOI:10.1016/bs.apha.2020.09.003
Source: Advances in Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research