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The Journal of Neuroscience, April 15, 2003, 23(8):3262
Lipid Rafts in the Maintenance of Synapses, Dendritic Spines, and
Surface AMPA Receptor Stability
Heike
Hering,
Chih-Chun
Lin, and
Morgan
Sheng
Picower Center for Learning and Memory, Howard Hughes Medical
Institute, and Departments of Brain and Cognitive Sciences and Biology,
Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Cholesterol/sphingolipid microdomains (lipid rafts) in the membrane
are involved in protein trafficking, formation of signaling complexes,
and regulation of actin cytoskeleton. Here, we show that lipid rafts
exist abundantly in dendrites of cultured hippocampal neurons, in which
they are associated with several postsynaptic proteins including
surface AMPA receptors. Depletion of cholesterol/sphingolipid leads to
instability of surface AMPA receptors and gradual loss of synapses
(both inhibitory and excitatory) and dendritic spines. The remaining
synapses and spines in raft-depleted neurons become greatly enlarged.
The importance of lipid rafts for normal synapse density and morphology
could explain why cholesterol promotes synapse maturation in retinal
ganglion cells (Mauch et al., 2001) and offers a potential link between
disordered cholesterol metabolism and the synapse loss seen in
neurodegenerative disease.
Key words:
cholesterol; sphingolipid; mevastatin; fumonisin
B1; endocytosis; cytoskeleton
Copyright © 2003 Society for Neuroscience 0270-6474/03/2383262-10$05.00/0
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