Is this bilayer expansion?

June 25, 2012

A clathrin heavy chain (chc1) mutant that is resistant to the SSRI antidepressant sertraline/Zoloft exhibits what appears to be bilayer expansion under both steady state and sertraline-treated conditions. It is also possible that the expansion of electron lucent (that is, white) material is occurring inside the lumen of amphisomes (aka autophagolysosomes).

What do you think? Please annotate in the comment thread below.

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  • Ethan Perlstein

    I think that the bilayer expansion is a lipid droplet intermediate. The question is: a structural intermediate in lipid droplet formation or degradation?

    • Itay Budin

      There’s models for droplet formation that basically mirror this; expansion of the bilayer due to localized build up of non-polar lipids. Once you have a droplet, I think it would be very challenging for it to degrade in any way outside of gradual dissolution from the surface (leading to a shrinking droplet). There’s a lot of interfacial energy, even with surfactants, so going from a droplet to a non-droplet morphology I would imagine is unlikely. So I would go with the former.

      • Ethan Perlstein

        Thanks for the feedback, Itay! I have shopped around these images to LD specialists and they all poo poo the lens formation model, though it seems if you’re going to base your argument on first principles your reasoning is more sound.

        What if cationic amphipaths like sertraline are accumulating the interfacial region of the LD monolayer? We don’t have any evidence from fractionation that hot sertraline is accumulating in LDs specifically, but we also can’t rule it out.