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Segregation of Nogo66 receptors into lipid rafts in rat brain and inhibition of Nogo66 signaling by cholesterol depletion
Author(s) -
Yu Weiying,
Guo Wei,
Feng Linyin
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.09.068
Subject(s) - lipid raft , neurite , microbiology and biotechnology , receptor , low affinity nerve growth factor receptor , raft , signal transduction , lipid microdomain , chemistry , myelin , biology , neurotrophin , biochemistry , neuroscience , membrane , central nervous system , in vitro , organic chemistry , copolymer , polymer
NogoA, a myelin‐associated component, inhibits neurite outgrowth. Nogo66, a portion of NogoA, binds to Nogo66 receptor (NgR) and induces the inhibitory signaling. LINGO‐1 and p75 neurotrophin receptor (p75), the low‐affinity nerve growth factor receptor, are also required for NogoA signaling. However, signaling mechanisms downstream to Nogo receptor remain poorly understood. Here, we observed that NgR and p75 were colocalized in low‐density membrane raft fractions derived from forebrains and cerebella as well as from cerebellar granule cells. NgR interacted with p75 in lipid rafts. In addition, disruption of lipid rafts by β‐methylcyclodextrin, a cholesterol‐binding reagent, reduced the Nogo66 signaling. Our results suggest an important role of lipid rafts in facilitating the interaction between NgRs and provide insight into mechanisms underlying the inhibition of neurite outgrowth by NogoA.