Cholesterol is an essential component of the plasma membrane. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), although a minor phospholipid, is the most abundant membrane phosphoinositide. Both lipids play key roles in a variety of cellular functions including as signalling molecules and major regulators of protein function. Studies on these important lipids have traditionally focused on the effect of each lipid individually. Accumulating evidence indicates, however, that these lipids may cross-regulate each others levels. Furthermore, it is becoming evident that cholesterol and PI(4,5)P2 can act together to modulate protein function and biological processes.
This book provides an overview of cellular functions and molecular mechanisms in which cholesterol and PI(4,5)P2 functions extend from parallel existence to crosstalk. It includes four sections. The first section introduces the reader to cholesterol and PI(4,5)P2. The second section demonstrates the mutual influence of these two critical lipids on their levels. The third section, divided into two parts, describes the co-modulation of protein function by cholesterol and PI(4,5)P2. The first part focuses on ion channels and the second - on lipid transfer proteins. The fourth section highlights other cellular processes at the intersection of cholesterol and PI(4,5)P2 involvement. Collectively, the book portrays the emerging relationship between cholesterol and PI(4,5)P2 in a broad array of biological systems and processes.
The book will be of interest to a wide audience of research scientists with an interest in the biophysical properties of lipids and the physiological consequences of their presence in biological systems, as well as graduate students, postdoctoral trainees, basic and clinical researchers, and pharmaceutical scientists. Specifically, the content will be relevant to researchers in the fields of biochemistry, molecular biophysics, pharmacology, neurobiology, cardiovascular biology, among others.
Provides a comprehensive overview of the current knowledge of the interplay between cholesterol and PI(4,5) P2
Provides an overview of the emerging relationship between cholesterol and PI(4,5)P2 in biological systems and processes
Discusses cellular processes and molecular mechanisms where lipid functions extend from parallel existence to crosstalk
Preface.- 1. Mutual influence of cholesterol and PI(4,5)P2 on their
levels.
Chapter 1. Mechanism of the regulation of plasma cholesterol levels
by PI(4,5)P2.
Chapter 2. Effect of cholesterol depletion on ciliary
PI(4,5)P2 levels.
Chapter
3. Impact of cholesterol on PI(4,5)P2 levels in
the brain.
Chapter 4. Alterations in PIP2 levels in the intracellular
cholesterol trafficking disorder NPC1.
Chapter 5. Targeting cholesterol
release and PI(4,5)P2 redistribution by the oral drug Miltefosine.-
2. Cross-talk between cholesterol and PI(4,5)P2 as a factor affecting protein
function.- A. Plasma membrane ion channels.
Chapter 6. From cross-talk to
synergism: the combined effect of cholesterol and PI(4,5)P2 on inwardly
rectifying potassium channels.
Chapter 7. Link between lysosomal cholesterol
and PI(4,5)P2 in the regulation of the voltage gated KCNQ2/3 potassium
channel.
Chapter 8. Cholesterol and PI(4,5)P2 binding to a ciliary membrane
transient receptor potential channel.
Chapter 9. Regulation of ell by
cholesterol and PI(4,5)P2.
Chapter 10. Cholesterol stimulates the
epithelial sodium channel in a PI(4,5)P2-dependent manner.
Chapter 11. Roles
of cholesterol and PI(4,5)P2 in store operated calcium entry.
Chapter
12. Roles of cholesterol and PI(4,5)P2 levels in the modulation of the
calcium activated chloride channel TMEM16A.- B. Lipid transport
proteins--Chapter 13. PI(4,5)P2 facilitates ORP1-mediated cholesterol
transport by promoting membrane targeting and cholesterol extraction.-
Chapter 14. Role of PI(4,5)P2 binding in ORP2-mediated cholesterol
distribution.
Chapter 15. PI(4,5)P2-dependent transport of cholesterol from
lysosomes to peroxisomes at lysosomeperoxisome contact sites.- 3. Cellular
processes at the intersection of cholesterol and PI(4,5)P2 involvement.-
Chapter 16. The insertion of the N-terminal domain of Gasdermin-D is
increased byPI(4,5)P2 and decreased by cholesterol.
Chapter 17. Cholesterol
promotes the cooperative interaction of formins with PI(4,5)P2 to initiate
actin nucleation.
Chapter 18. Cooperation between cholesterol and PI(4,5)P2
in the regulation of Engrailed-2 homeoprotein intercellular trafficking.-
Chapter 19. Cholesterol and PI(4,5)P2 as a membrane nanoplatform for HIV
assembly.
Chapter 20. Role of Cholesterol and PI(4,5)P2 in the localization
of the HIV-1 structural polyprotein Gag to the plasma membrane.
Avia Rosenhouse-Dantsker, DSc, is a Clinical Associate Professor at the University of Illinois at Chicago. Her research background ranges from quantum theory and computational biology to biophysical chemistry, molecular biology and electrophysiology. Her current research employs experimental and computational approaches to elucidate structural and functional mechanisms of protein modulation with a special emphasis on the co-modulation of ion channels by lipids (e.g., cholesterol, phosphoinositides, and others).
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