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Sci. STKE, Vol. 2006, Issue 321, pp. pe6, 7 February 2006
[DOI: 10.1126/stke.3212006pe6]

Role of Docosahexaenoic Acid in Neuronal Plasma Membranes

John A. Glomset*

Howard Hughes Medical Institute, Departments of Medicine and
Biochemistry, and Regional Primate Research Center, University of
Washington, Seattle, WA 98195-7370, USA.


Summary: The omega-3 fatty acid docosahexaenoic acid (DHA n-3)
has long been known to be a major component of phosphoglycerides in
the gray matter of mammalian brains. Furthermore, early studies of
synaptosomes that had been isolated from gray matter showed that the
plasma membranes of the synaptosomes contained DHA n-3 that was
selectively esterified to phosphatidylethanolamine,
plasmenylethanolamine (alkenylacyl-glycero-phosphorylethanolamine),
and phosphatidylserine. In contrast, the phosphatidylcholine in
these membranes contained esterified oleic acid, and the
sphingomyelin and glycolipids in the membranes contained
amide-linked stearic acid instead of a mixture of this acid with
other, amide-linked fatty acids. The full implications of this
unusual distribution of lipid head groups, esterified fatty acids,
and amide-linked fatty acids are unclear, but the phosphoglycerides
and sphingosine-containing lipids appear to be distributed
asymmetrically between the two leaflets of the plasma membrane lipid
bilayer and are likely to contribute to a dynamic lipid
substructure. Because very few neuronal plasma membranes have been
isolated and characterized to date, a major challenge for the future
will be to investigate the composition of the lipid bilayers of
different neuronal plasma membranes and identify effects of DHA
n-3-containing phosphoglycerides on the ability of the plasma
membranes to perform their many different functions. The aim of this
Perspective is to stimulate further work in this important area by
discussing recent evidence related to the role of neuronal plasma
membrane phosphoglycerides in cell signaling.



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