Review
Plasma membranes as heat stress sensors: From lipid-controlled molecular switches to therapeutic applications☆☆

https://doi.org/10.1016/j.bbamem.2013.12.015Get rights and content
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Highlights

  • Mild heat stress (within typical fever ranges) is sensed by rearrangement of plasma membrane nanoplatforms.

  • Cell profiling, lipidomics and computer modeling are tools to study membrane events

  • HSF1 integrates stress signals that originate from the plasma membrane

  • Membrane lipid therapy offers a timely and important application of agents that can modify stress responses

Abstract

The classic heat shock (stress) response (HSR) was originally attributed to protein denaturation. However, heat shock protein (Hsp) induction occurs in many circumstances where no protein denaturation is observed. Recently considerable evidence has been accumulated to the favor of the “Membrane Sensor Hypothesis” which predicts that the level of Hsps can be changed as a result of alterations to the plasma membrane. This is especially pertinent to mild heat shock, such as occurs in fever. In this condition the sensitivity of many transient receptor potential (TRP) channels is particularly notable. Small temperature stresses can modulate TRP gating significantly and this is influenced by lipids. In addition, stress hormones often modify plasma membrane structure and function and thus initiate a cascade of events, which may affect HSR. The major transactivator heat shock factor-1 integrates the signals originating from the plasma membrane and orchestrates the expression of individual heat shock genes. We describe how these observations can be tested at the molecular level, for example, with the use of membrane perturbers and through computational calculations. An important fact which now starts to be addressed is that membranes are not homogeneous nor do all cells react identically. Lipidomics and cell profiling are beginning to address the above two points. Finally, we observe that a deregulated HSR is found in a large number of important diseases where more detailed knowledge of the molecular mechanisms involved may offer timely opportunities for clinical interventions and new, innovative drug treatments. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.

Abbreviations

AA
arachidonic acid
APAP
acetaminophen
aSMase
acid sphingomyelinase
ATP
adenosine triphosphate
BA
benzyl alcohol
BM
bimoclomol
CaMKII
calmodulin kinase II
Cdase
ceramidase
CHO
Chinese hamster ovary
CHOL
cholesterol
CRA
crotonaldehyde
DAG
diacylglycerol
DMPC
1,2-dimyristoyl-sn-glycero-3-phosphocholine
DPH
1,6-diphenyl-1,3,5-hexatriene
EGFR
epidermal growth factor receptor
ERK1/2
extracellular-signal-regulated kinase
FRET
fluorescence resonance energy transfer
GCS
glucosylceramide synthase
GFP
green fluorescent protein
GFR
growth factor receptor
GlcCer
glucosylceramide
GPI
glycophosphatidylinositol
GR
glucocorticoid receptor
GSK3
glycogen synthase kinase-3
HNE
4-hydroxynonenal
HSF1
heat shock factor 1
HSP
heat shock protein
HSR
heat shock response
IP3
inositol trisphosphate
LB
luria broth
Ld
liquid disordered
Lo
liquid ordered
LPA
lysophosphatidic acid
LPA
alpha lipoic acid
LPC
lysophosphatidylcholine
LPS
lysophosphatidylserine
MALDI
matrix-assisted laser desorption/ionization
MAPK
mitogen-activated protein kinase
MBCD
methyl-β-cyclodextrin
MD
molecular dynamics
MPS
membrane physical state
mTOR
target of rapamycin
NADA
N-arachidonoyl-dopamine
NPN
1-N-phenylnaphthylamine
PhA
phenethyl alcohol
PHB
poly-(R)-3-hydroxybutyrate
PI3K
phosphatidylinositol-3-kinase
PI4P
phosphatidylinositol 4-phosphate
PIP2
phosphatidylinositol 4,5-bisphosphate
PIP3
phosphatidylinositol-3,4,5-triphosphate
PKA
protein kinase A
PKC
protein kinase C
PLA2
phospholipase A2
PLC
phospholipase C
PLD
phospholipase D
POPC
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
POPE
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine
S1P
sphingosine-1-phosphate
SFA
saturated fatty acids
SGT
glucosyltransferase
SK1
sphingosine kinase 1
SM
sphingomyelin
SPC
sphingosylphosphorylcholine
TIRF
total internal reflection fluorescence
TOCCSL
Thinning Out Clusters while Conserving the Stoichiometry of Labeling
TRP
transient receptor potential channel
UFA
unsaturated fatty acids
YFP
yellow fluorescent protein

Keywords

Lipid raft
TRP channel
Heat shock response
Stress hormone
Cell-to-cell heterogeneity
Lipidomics
Membrane lipid therapy

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☆☆

This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.