Cholesterol Regulation of Ion Channels and Receptors

311 Pages·2012·3.998 MB·English

CHOLESTEROL
REGULATION OF ION
CHANNELS
AND RECEPTORS
CHOLESTEROL
REGULATION OF ION
CHANNELS
AND RECEPTORS
Editedby
IRENA LEVITAN
FRANCISCO J. BARRANTES
AJOHNWILEY&SONS,INC.,PUBLICATION
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LibraryofCongressCataloging-in-PublicationData:
Cholesterolregulationofionchannelsandreceptors/editedbyIrenaLevitan,
FranciscoJ.Barrantes.
p.;cm.
Includesbibliographicalreferencesandindex.
ISBN978-0-470-87432-5(cloth)
I.Levitan,Irena.II.Barrantes,FranciscoJ.,1944-
[DNLM:1. Cholesterol–metabolism.2. IonChannels–metabolism.3. Membrane
Proteins–metabolism. QU95]
612.1(cid:1)2–dc23
2012011095
PrintedintheUnitedStatesofAmerica
ISBN:9780470874325
10987654321
CONTENTS
FOREWORD vii
PREFACE ix
CONTRIBUTORS xi
I CHOLESTEROL REGULATION OF MEMBRANE
PROPERTIES 1
1 CHOLESTEROLTRAFFICKINGANDDISTRIBUTION
BETWEENCELLULARMEMBRANES 3
DanielWu¨stner,LukaszMichaelSolanko,andFrederikW.Lund
2 CHOLESTEROLREGULATIONOFMEMBRANEPROTEIN
FUNCTIONBYCHANGESINBILAYERPHYSICAL
PROPERTIES—ANENERGETICPERSPECTIVE 27
JensA.LundbækandOlafS.Andersen
II CHOLESTEROL REGULATION OF ION CHANNELS 45
3 INSIGHTSINTOSTRUCTURALDETERMINANTSOF
CHOLESTEROLSENSITIVITYOFKIRCHANNELS 47
AviaRosenhouse-DantskerandIrenaLevitan
4 ROLEOFLIPIDRAFTSINTHEREGULATIONOF
STORE-OPERATEDCA2+ CHANNELS 69
HweiL.OngandInduS.Ambudkar
v
vi CONTENTS
5 CHOLESTEROLREGULATIONOFCARDIACION
CHANNELS 91
EliseBalse,Ste´phaneHatem,andStanleyNattel
6 DIFFERENTIALCONTRIBUTIONOFBKSUBUNITSTO
NONGENOMICREGULATIONOFCHANNELFUNCTION
BYSTEROIDS 109
AlexM.Dopico,AnnaN.Bukiya,andAdityaK.Singh
7 REGULATIONOFK+ CHANNELSBY
CHOLESTEROL-RICHMEMBRANEDOMAINSINTHE
IMMUNESYSTEM 135
Nu´riaComesandAntonioFelipe
8 INDIRECTCHANNELREGULATIONBYCHOLESTEROL:
THEROLEOFCAVEOLAEANDCAVEOLINSIN
REGULATINGK CHANNELFUNCTION 161
ATP
CarolineDart
III CHOLESTEROL REGULATION OF RECEPTORS 181
9 REGULATIONOFTHENICOTINICACETYLCHOLINE
RECEPTORBYCHOLESTEROLASABOUNDARYLIPID 183
FranciscoJ.Barrantes
10 SPECIFICANDNONSPECIFICREGULATIONOFGPCR
FUNCTIONBYCHOLESTEROL 205
GeraldGimplandKatjaGehrig-Burger
11 STRUCTURALINSIGHTSINTOCHOLESTEROL
INTERACTIONSWITHG-PROTEIN-COUPLED
RECEPTORS 231
JeremiahS.Joseph,EnriqueE.Abola,andVadimCherezov
12 MEMBRANECHOLESTEROL:IMPLICATIONSIN
RECEPTORFUNCTION 255
SandeepShrivastavaandAmitabhaChattopadhyay
13 THEROLEOFCHOLESTEROLANDLIPIDRAFTSIN
REGULATIONOFTLRRECEPTORS 273
RuxanaT.Sadikot
INDEX 281
FOREWORD
CHOLESTEROL:BILAYERSANDCELLS
Cholesterol’sfunctionincellsisacomplextopicthatdeservesabroaderperspec-
tive than is usually taken. This volume is introduced by two chapters, apparently
poles apart in subject and approach, which widen our perspective and point the
way to still other ways of considering cholesterol’s function in cells.
The introductory chapter places cholesterol in the context of cell metabolism
and trafficking of metabolites to membranes. This cell scale discussion broadens
our perspective so that we see cholesterol as one of many small molecules,
synthesized or taken up by cells, which must be trafficked or stored so that their
levelisoptimizedandtheyareavailableforinteractionwiththeirproteinpartners.
Thesecondchapter,incontrasttothefirst,looksatthephysicsandenergeticsof
cholesterol effects on membrane proteins. Although this is an enormous contrast
inscaleandapproach,thischaptertoobroadensourperspectivebyclassifyingall
possible effects of cholesterol on protein function into just two types: the effects
on energetics of proteins themselves, with the binding of cholesterol affecting
conformational changes of a protein, and effects on the energetics of the lipid
bilayer in which the protein is embedded. Although this useful dichotomy is
probably insufficient to characterize all cholesterol effects on membrane protein
function,itcertainlydirectsourviewtothegeneralandawayfromtheparticular
protein, channel or receptor, discussed in subsequent chapters. Indeed, I found
that it framed my view of all of these other chapters.
Collectively, the reviews presented here, on the cholesterol requirements for
channel and receptor (GCPR) function, pass beyond the dichotomy of choles-
terol effects on protein energetics and protein effects on lipid bilayer energetics
vii
viii FOREWORD
to suggest a third major function of cholesterol in the localization and activity of
membraneproteins.Atitsleastspecific,thisfunctionischaracterizedasarequire-
ment for the environment of a lipid raft. This environment likely concentrates
other lipids and proteins that are required for protein function. While the selec-
tive localization of proteins and lipids ultimately depends on the physics of the
bilayer, it is manifest by changes in chemistry, for example, in the levels of
membrane-associated signaling lipids and other partners required for function of
channels and receptors.
Plasma membrane associations modulated likely by cholesterol are shown
to modulate receptor trafficking as well as ultimate localization. The chapters
describingeffectsofcholesterolmodulationontraffickingandlocalizationfurther
broaden our perspective on cholesterol requirements for cell function. They go
well beyond the limitations of model membrane systems; another reminder of
the difficulties of translating results in simple lipid mixtures near equilibrium
to the complexities of living cells far from equilibrium. However, this does not
imply abandoning model membranes for the study of cholesterol requirements
for cell function. Rather it suggests development of experimental new models.
These will be more complex than those used in the past but nevertheless are
simplifications and clarifications of native cell membranes. We need the detail
and quantification that model membranes yield to prepare the canvas and prime
the surface on which the field will paint the big picture and the wide perspective
of the dance of membrane lipids and proteins.
Michael Edidin
DepartmentsofMedicine,MaterialsScienceandPathology,
JohnsHopkinsUniversity,Baltimore,MD
Baltimore,July2011
PREFACE
Over the last decade, there has been an explosion of studies focusing on the role
of cholesterol in the regulation of ion channels and membrane receptors, many
of which have shown that changes in the level of membrane cholesterol regulate
a variety of ion channels and receptors belonging to almost all known families
oftheseproteins.Furthermore,multipletypesofionchannelsandreceptorshave
beenshowntoexhibitatendencytopartitionintospecificmembranedomainsthat
arecholesterolenriched.Itbecomesincreasinglyclear,therefore,thatcholesterol
is a major regulator of ion channel and receptor function.
Increased levels of cholesterol in blood represent a major risk factor for the
development of atherosclerosis, heart attack, and stroke, as a consequence of
which cholesterol sensitivity of ion channels and receptors is expected to play
a key role in the impairment of numerous physiological processes, including
excitability of cardiomyocytes, vascular smooth muscle cells, and neurons, as
well as dysfunction of endothelial cells and impairment of immune function. It
is critical, therefore, to understand the mechanisms of cholesterol regulation of
ion channels and receptors in order to facilitate the development of new ther-
apeutic strategies to alleviate the impact of pathological cholesterol conditions.
In this book, we bring together the most up-to-date knowledge about the role of
cholesterol in the regulation of ion channels and receptors and the pathological
implications of its effects.
TheideaforthisbookoriginatedinthesymposiumCholesterolasaRegulator
ofChannelandReceptorFunction that we organized 2 years ago for the Annual
Meeting of the American Biophysical Society, held in Boston in 2009. The
speakers at the symposium presented a diversity of complementary points of
view about the mechanisms underlying cholesterol action on ion channels and
ix
x PREFACE
receptors.Inthisbook,weextendthetopicstoacomprehensivecriticaloverview
of the field. We are very grateful to our publishing editor, Dr. Anita Lekhwani,
who first approached us with the idea of developing our symposium into a full
book and who has been tremendously helpful at all stages of the project.
Among the major concepts discussed are regulation of ion channels and
receptors by the physical properties of lipid bilayers and the mismatch between
the hydrophobic domains of the proteins and the hydrophobic interior of the
membrane-specificcholesterol–proteininteractionsintheregulationofionchan-
nels and receptors and regulation of these proteins by aggregation into multi-
protein signaling platforms (“rafts”). Several of the chapters present the latest
insights into the structural determinants of cholesterol sensitivity of ion channels
andreceptorsandanalyzeputativecholesterolbindingsiteswithspecialemphasis
on the physiological role of this sensitivity in different cell types. The combined
essays present a thorough analysis of current thinking and breakthrough discov-
eries relating to cholesterol regulation of ion channels and receptors, leaving the
debate wide open to further advances in the field.
Irena Levitan
Francisco J. Barrantes
CONTRIBUTORS
Enrique E. Abola, Department of Molecular Biology, The Scripps Research
Institute, La Jolla, CA
Indu S. Ambudkar, Molecular Physiology and Therapeutics Branch, NIDCR,
NIH, Bethesda, MD
Olaf S. Andersen, Department of Physiology and Biophysics, Weill Cornell
Medical College, New York, NY
EliseBalse,Faculte´deme´decinePitie´-Salpe´trie`re,INSERMUMRS-956,Paris,
France; Universite´ Pierre et Marie Curie, Sorbonne Universite´s, Paris, France
Francisco J. Barrantes, Facultad de Ciencias Me´dicas, Pontificia Universi-
dad Cato´lica Argentina, Aires, Argentina
Anna N. Bukiya, Department of Pharmacology, The University of Tennessee
Health Science Center, Memphis, TN
AmitabhaChattopadhyay,CentreforCellularandMolecularBiology,Coun-
cil of Scientific and Industrial Research, Hyderabad, India
Vadim Cherezov, Department of Molecular Biology, The Scripps Research
Institute, La Jolla, CA
Nu´ria Comes, Departament de Bioqu´ımica i Biologia Molecular, Institut de
Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain
Caroline Dart, Institute of Integrative Biology, University of Liverpool,
Liverpool, United Kingdom
xi