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ABHD4 Regulates Multiple Classes of N‑Acyl Phospholipids in the Mammalian Central Nervous System
journal contribution
posted on 2015-04-21, 00:00 authored by Hyeon-Cheol Lee, Gabriel
M. Simon, Benjamin F. CravattN-Acyl phospholipids are atypical components of
cell membranes that bear three acyl chains and serve as potential
biosynthetic precursors for lipid mediators such as endocannabinoids.
Biochemical studies have implicated ABHD4 as a brain N-acyl phosphatidylethanolamine (NAPE) lipase, but in vivo evidence for this functional assignment is lacking. Here, we describe
ABHD4–/– mice and their characterization
using untargeted lipidomics to discover that ABHD4 regulates multiple
classes of brain N-acyl phospholipids. In addition
to showing reductions in brain glycerophospho-NAEs (GP-NAEs) and plasmalogen-based
lyso-NAPEs (lyso-pNAPEs), ABHD4–/– mice exhibited
decreases in a distinct set of brain lipids that were structurally
characterized as N-acyl lysophosphatidylserines (lyso-NAPSs).
Biochemical assays confirmed that NAPS lipids are direct substrates
of ABHD4. These findings, taken together, designate ABHD4 as a principal
regulator of N-acyl phospholipid metabolism in the
mammalian nervous system.