Related Experiment Video
Updated: May 29, 2026
Development of an Ethanol-induced Fibrotic Liver Model in Zebrafish to Study Progenitor Cell-mediated Hepatocyte Regeneration
Published on: May 13, 2016
Ethanol causes the redistribution of L1 cell adhesion molecule in lipid rafts
Ningfeng Tang1, Benjamin Farah, Min He
1Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21209, USA.
Insights
Ethanol exposure disrupts the association of L1 cell adhesion molecule (L1) with lipid rafts, inhibiting neurite outgrowth. This mechanism may underlie fetal alcohol spectrum disorder neurotoxicity.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Fetal alcohol spectrum disorder (FASD) affects approximately 1% of live births.
- Similarities between fetal alcohol syndrome and L1 cell adhesion molecule (L1) mutations suggest L1 is a target of ethanol neurotoxicity.
- Ethanol inhibits L1-mediated neurite outgrowth at pharmacologic concentrations, potentially via lipid raft disruption.
Purpose of the Study:
- To investigate the hypothesis that ethanol impairs L1 association with lipid rafts.
- To elucidate the mechanism by which ethanol inhibits L1-mediated neurite outgrowth.
Main Methods:
- In vitro examination of L1 and lipid raft association following ethanol treatment.
- Assessment of L1-mediated neurite outgrowth in cerebellar granule neurons with disrupted lipid rafts using methyl-beta-cyclodextrin.
- Evaluation of ethanol's effect on L1-Fc mediated neurite outgrowth.
Main Results:
- In vitro, L1, but not N-cadherin, shifted into lipid rafts upon exposure to 25 mM ethanol.
- Ethanol concentrations causing this shift align with those inhibiting L1-mediated neurite outgrowth.
- Disruption of lipid rafts in cerebellar granule neurons reduced L1-mediated neurite outgrowth to an ethanol-insensitive background rate.
Conclusions:
- Ethanol may inhibit L1-mediated neurite outgrowth by impeding L1 trafficking through lipid rafts.
- These findings provide a potential mechanism for ethanol's developmental neurotoxicity in FASD.
- Targeting lipid raft-mediated L1 function could offer therapeutic avenues for FASD.
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.
More Related Videos
Related Concept Videos
01:26Membrane Fluidity
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:21Cell Polarization by Rho Proteins