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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Tuesday Speaker Abstracts
26
Targeting Proteins to Lipid Rafts: Mechanisms and Consequences
Anne K. Kenworthy
,
Vanderbilt School of Medicine, Nashville, TN, USA.
How proteins and lipids cooperate to form functional domains remains a major question in
biology. Here, I will discuss our recent studies of how proteins interact with raft-associated lipids
and the functional consequences of these interactions. First, I will discuss how transmembrane
proteins are targeted to rafts, focusing on the 99 residue transmembrane C-terminal domain
(C99) of amyloid precursor protein as a model. Association of C99 with cholesterol-rich
membrane raft domains is thought to promote cleavage of C99 to release the Alzheimer’s
disease-promoting amyloid-β (Aβ) polypeptide. By reconstituting C99 into model membrane
systems, we are currently testing the hypothesis that C99 has an intrinsic affinity for raft-like
liquid ordered domains imparted by its ability to specifically bind to cholesterol. Second, I will
discuss how the bacterial toxin cholera toxin targets rafts as a mechanism to enter cells via
endocytosis. Using cell membrane-derived systems and living cells, we are currently examining
the role of toxin-induced raft crosslinking in the induction of membrane curvature and toxin
uptake.