Posted by The most interesting finding of Crui et al. in their recently published paper [1] for the readers of the Cyclodextrin News blog that treatment of melanoma cells by methyl beta-CD reduced not only the plasma membrane cholesterol content, but also decreased lysophosphatidylcholine and phosphatidic acid levels according to lipidomics analysis. Imaging fluorescent correlation spectroscopy marked a modulated lateral diffusion constant of fluorescently labelled cholesterol in plasma membrane during cholesterol deprived conditions.
The aim of the work was to compare the effect of methyl beta-CD- and nystatin-induced cholesterol modulations on stress-activated expression of some representative heat shock proteins (HSPs). Being chaperoning proteins, HSPs recognize and prevent non-native protein conformations from forming deleterious protein aggregates during stress and, once the stressful event passed, assist in refolding or proteasomal degradation, depending on the extent of harmful exposure. The heat shock response regulates induction of stress/heat shock proteins to preserve proteostasis during cellular stress.
The authors demonstrated impaired heat-induced HSP expression levels upon targeted plasma membrane modulation in B16-F10 cells. These data not only highlight the involvement of plasma membrane integrity in heat shock response but also suggest that altered dynamics of specific cholesterol pools could represent a mechanism
to fine tune HSP expression.
[1] Tim Crul, Balint Csoboz, Imre Gombos, Annamaria Marton, Maria Peter,Gabor Balogh, Csaba Vizler, Lajos Szente and Laszlo Vigh (2020) Modulation of Plasma Membrane Composition and Microdomain Organization Impairs Heat Shock Protein Expression in B16-F10 Mouse Melanoma Cells. Cells 9, 951; https://doi.org/10.3390/cells9040951