Transport of plasma membrane‐derived cholesterol and the function of Niemann‐Pick C1 protein

  title={Transport of plasma membrane‐derived cholesterol and the function of Niemann‐Pick C1 protein},
  author={Volker Wiegand and Ta-Yuan Chang and Jerome F Strauss and Falk Fahrenholz and Gerald Gimpl},
  journal={The FASEB Journal},
To visualize the intracellular transport of plasma membrane‐derived cholesterol under physiological and pathophysiological conditions, a novel fluorescent cholesterol analog, 6‐dansyl cholestanol (DChol), has been synthesized. We present several lines of evidence that DChol mimics cholesterol. The cholesterol probe could be efficiently incorporated into the plasma membrane via cyclodextrin‐donor complexes. The itinerary of DChol from the plasma membrane to the cell was studied to determine its… 
Use of dansyl-cholestanol as a probe of cholesterol behavior in membranes of living cells[S]
DChol sensed a unique, relatively more mobile microenvironment for cholesterol in plasma membrane cholesterol- rich microdomains, consistent with the known, more rapid exchange dynamics of cholesterol from cholesterol-rich than -poor microdomain.
Cholesterol Reporter Molecules
Different approaches to detect cholesterol in vitro and in vivo are described and the features of the different cholesterol reporter molecules are critically discussed with a special focus on recent imaging approaches.
Intracellular Cholesterol Transport
Intracellular cholesterol transport is essential for the maintenance of cholesterol homeostasis. Many aspects of cholesterol metabolism are well-known, including its synthesis in the endoplasmic
Deficiency of a Niemann-Pick, Type C1-related Protein in Toxoplasma Is Associated with Multiple Lipidoses and Increased Pathogenicity
A role is ascribed for TgNCR1 in lipid homeostasis in Toxoplasma, which has lost the ability to control the intracellular levels of several lipids, which subsequently results in the stimulation of lipid storage, membrane biosynthesis and parasite division.
Fluorescent Sterols and Cholesteryl Esters as Probes for Intracellular Cholesterol Transport
It is shown that P-sterol esters inserted into low-density lipoprotein can be tracked in the fibroblasts of Niemann–Pick disease using high-resolution deconvolution microscopy.
Designing fluorescent probes for the study of intracellular cholesterol metabolism
Three new synthetic fluorophores, Fp1-Fp3, were provided by the Institute of Biotechnology of the Czech Academy of Sciences and their applicability in the fluorophore-labeling of cholic acid and methyl lithocholate was investigated.
Effects of 25-Hydroxycholesterol on Cholesterol Esterification and Sterol Regulatory Element-binding Protein Processing Are Dissociable
This study addressed whether or not cholesterol esterification necessarily reflects cholesterol movement to the cholesterol homeostatic machinery in the ER as determined by SREBP processing and questioned the security of previous work that has inferred cholesterol transport to the ER regulatory pool based solely on cholesterol Esterification.
Cholesterol binding is a prerequisite for the activity of the steroidogenic acute regulatory protein (StAR).
A proposed molecular model indicates that StAR can readily bind to cholesterol with an apparent affinity that commensurates with monomeric cholesterol solubility in water and the mutation F267Q reduced the biological activity of StAR.
Targeted Mutation of the MLN64 START Domain Causes Only Modest Alterations in Cellular Sterol Metabolism*
The StAR-related lipid transfer (START) domain, first identified in the steroidogenic acute regulatory protein (StAR), is involved in the intracellular trafficking of lipids. Sixteen mammalian START


Fate of Endogenously Synthesized Cholesterol in Niemann-Pick Type C1 Cells*
Results using the inhibitorN-butyldeoxynojirimycin, which depletes cellular complex glycosphingolipids, demonstrates that the cholesterol trafficking defect in NPC1 cells is not caused by ganglioside accumulation.
Role of Niemann-Pick Type C1 Protein in Intracellular Trafficking of Low Density Lipoprotein-derived Cholesterol*
It is found that the initial movement of low density lipoprotein (LDL)-derived cholesterol to the plasma membrane (PM) did not require NPC1, but after reaching the PM and subsequent internalization, cholesterol trafficking back to the PM did involve NPC1.
Intracellular Trafficking of Cholesterol Monitored with a Cyclodextrin*
Biochemical and cytochemical studies reveal that cyclodextrin specifically removes plasma membrane cholesterol, and attenuated esterification of lysosomal cholesterol in Niemann-Pick C cells reflects defective translocation of cholesterol to the plasma membrane that may be linked to abnormal Golgi trafficking.
Rapid nonvesicular transport of sterol between the plasma membrane domains of polarized hepatic cells.
It is concluded that sterol shuttles rapidly among the plasma membrane domains and other membrane organelles and that this nonvesicular pathway includes fast transbilayer migration.
Sterol-modulated Glycolipid Sorting Occurs in Niemann-Pick C1 Late Endosomes*
It is concluded that the NPC1 compartment is a dynamic, sterol-modulated sorting organelle involved in the trafficking of plasma membrane-derived glycolipids as well as plasma membrane and endocytosed LDL cholesterol.
Circulation of Cholesterol between Lysosomes and the Plasma Membrane*
It is concluded that cholesterol circulates bidirectionally between the plasma membrane and lysosomes, and the massive accumulation of lysOSomal cholesterol in the perturbed cells does not appear to reflect disabled lysoomal transport but rather the formation of lYSosomes modified for lipid storage, i.e. lamellar bodies.
Dissecting the role of the golgi complex and lipid rafts in biosynthetic transport of cholesterol to the cell surface.
The results provide evidence for the partial contribution of the Golgi complex to the transport of newly synthesized cholesterol to the cell surface and suggest that detergent-resistant membranes are involved in the process.
Vesicular and Non-vesicular Sterol Transport in Living Cells
It is proposed that a large portion of intracellular cholesterol is localized in the ERC, and this pool might be important in maintaining cellular cholesterol homeostasis.
Cholesterol Movement in Niemann-Pick Type C Cells and in Cells Treated with Amphiphiles*
It is shown that the rate of movement of cholesterol from lysosomes to plasma membranes in NP-C cells is at least as great as normal, as was also found previously for amphiphile-treated cells, and the lysOSomes in these cells filled with plasma membrane cholesterol in the absence of lipoproteins.
Cholesterol domains in biological membranes.
The size, dynamics and distribution of cholesterol domains within membranes not only regulate cholesterol efflux/influx but also modulate plasma membrane protein functions and receptor-effector coupled systems.