title: Ethanol causes the redistribution of L1 cell adhesion molecule in lipid rafts.
abstract: Fetal alcohol spectrum disorder is estimated to affect 1% of live births. The similarities between children with fetal alcohol syndrome and those with mutations in the gene encoding L1 cell adhesion molecule (L1) implicates L1 as a target of ethanol developmental neurotoxicity. Ethanol specifically inhibits the neurite outgrowth promoting function of L1 at pharmacologic concentrations. Emerging evidence shows that localized disruption of the lipid rafts reduces L1-mediated neurite outgrowth. We hypothesize that ethanol impairment of the association of L1 with lipid rafts is a mechanism underlying ethanol's inhibition of L1-mediated neurite outgrowth. In this study, we examine the effects of ethanol on the association of L1 and lipid rafts. We show that, in vitro, L1 but not N-cadherin shifts into lipid rafts following treatment with 25 mM ethanol. The ethanol concentrations causing this effect are similar to those inhibiting L1-mediated neurite outgrowth. Increasing chain length of the alcohol demonstrates the same cutoff as that previously shown for inhibition of L1-L1 binding. In addition, in cerebellar granule neurons in which lipid rafts are disrupted with methyl-beta-cyclodextrin, the rate of L1-mediated neurite outgrowth on L1-Fc is reduced to background rate and that this background rate is not ethanol sensitive. These data indicate that ethanol may inhibit L1-mediated neurite outgrowth by retarding L1 trafficking through a lipid raft compartment.
authors: Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21209, USA.
authors: Ningfeng
authors: N
authors: Tang
authors: Benjamin
authors: B
authors: Farah
authors: Min
authors: M
authors: He
authors: Stephanie
authors: S
authors: Fox
authors: Alfred
authors: A
authors: Malouf
authors: Yoav
authors: Y
authors: Littner
authors: Cynthia F
authors: CF
authors: Bearer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000440:Butanols / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D021962:Membrane Microdomains / Q000187:drug effects*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D000440:Butanols; D002492:Central Nervous System Depressants; D039842:Neural Cell Adhesion Molecule L1; D014404:Tubulin; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000431:Ethanol