1 research outputs found
Multifunctional Proximity Labeling Strategy for Lipid Raft-Specific Sialic Acid Tracking and Engineering
Lipid raft-specific glycosylation has been implicated
in many biological
processes, including intracellular trafficking, cell adhesion, signal
transduction, and host–pathogen interactions. The major predicament
in lipid raft-specific glycosylation research is the unavailability
of tools for tracking and manipulating glycans on lipid rafts at the
microstructural level. To overcome this challenge, we developed a
multifunctional proximity labeling (MPL) platform that relies on cholera
toxin B subunit to localize horseradish peroxidase on lipid rafts.
In addition to the prevailing electron-rich amino acids, modified
sialic acid was included in the horseradish peroxidase-mediated proximity
labeling substrate via purposefully designed chemical transformation
reactions. In combination with sialic acid editing, the self-renewal
of lipid raft-specific sialic acid was visualized. The MPL method
enabled tracking of lipid raft dynamics under methyl-β-cyclodextrin
and mevinolin treatments; in particular, the alteration of lipid rafts
markedly affected cell migration. Furthermore, we embedded functional
molecules into the method and implemented raft-specific sialic acid
gradient engineering. Our novel strategy presents opportunities for
tailoring lipid raft-specific sialic acids, thereby regulating interactions
associated with lipid raft regions (such as cell–virus and
cell–microenvironment interactions), and can aid in the development
of lipid raft-based therapeutic regimens for tumors