title: Oligodendroglial process formation is differentially affected by modulating the intra- and extracellular cholesterol content.
abstract: Cholesterol is an essential component of eukaryotic plasma membranes and plays an important role in membrane organization and signaling processes. It is the major lipid component of detergent resistant caveolin-1 containing rafts which previously had been reported as a platform for nerve growth factor (NGF) signaling in oligodendrocytes (OL). Surprisingly, a knockdown of caveolin-1 attenuated the process formation of OL (Schmitz et al. J Neurosci Res 88:572-588, 2010), for which a loss of cholesterol could be responsible. In the present report, we could show that a caveolin-1 knockdown resulted in an elevation of cellular cholesterol level; it may indicate an important role of caveolin-1 in cholesterol trafficking to the plasma membrane. Treatment with exogenous PEG cholesterol, which was incorporated to the plasma membrane, supported oligodendroglial process formation, in particular when OL were stimulated by NGF. In this context we have found that OL express NPC1L1 (Niemann-Pick disease type C1-Like 1) which could modulate cholesterol uptake. In contrast, depletion of membrane-bound cholesterol diminished NGF-induced process formation concomitant with a reduced activity of p42/44 mitogen-activated protein kinases.
authors: Max-Planck Institute of Experimental Medicine, RU Neural Regeneration, Hermann-Rein-Straße 3, 37075, Goettingen, Germany. matthias.schmitz@med.uni-goettingen.de
authors: Matthias
authors: M
authors: Schmitz
authors: Sandra C
authors: SC
authors: Signore
authors: Inga
authors: I
authors: Zerr
authors: Hans H
authors: HH
authors: Althaus
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D021941:Caveolae / Q000378:metabolism / Q000648:ultrastructure; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002449:Cell Aggregation; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D045604:Extracellular Fluid / Q000737:chemistry; D007424:Intracellular Fluid / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000502:physiology; D009836:Oligodendroglia / Q000378:metabolism / Q000648:ultrastructure*; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D051242:Caveolin 1; D008563:Membrane Lipids; D026901:Membrane Transport Proteins; D034741:RNA, Small Interfering; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C095164:poly(oxyethylene) cholesteryl ether; D011092:Polyethylene Glycols; D020932:Nerve Growth Factor; D002784:Cholesterol