Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles

Thiele, Christoph; Hannah, Matthew J.; Fahrenholz, Falk; Huttner, Wieland B.

doi:10.1038/71366

Cited by 527 publications

(496 citation statements)

References 47 publications

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“…Cells were labelled with the different photoactivatable precursors as described 7,8 . Briefly, cells were washed with PBS, followed by addition of freshly prepared delipidated medium containing lipid precursors.…”

Section: Methods Summarymentioning

confidence: 99%

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Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain

Contreras

Ernst

Haberkant

et al. 2012

Nature

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This is an accepted version of a paper published in Nature. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination.Citation for the published paper: von Heijne, G., Contreras, X., Ernst, A., Haberkant, P., Björkholm, P. et al. (2012) "Molecular recognition of a single sphingolipid species by a protein's transmembrane domain" Nature, 481 (7382): 525-529 URL: http://dx

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Section: Methods Summarymentioning

confidence: 99%

“…1) 6 . Lipid crosslinking 7,8 revealed a strong sphingolipid labelling of p24 (Fig. 1a-b, see also Supplementary Fig.…”

mentioning

confidence: 94%

Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain

Contreras

Ernst

Haberkant

et al. 2012

Nature

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349

320

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“…To complex [ 3 H]-photo-CH with MBCD 200 μl of [ 3 H]-photo-CH (2 mCi/ml) in ethanol, in a sterile glass vial, was dried down in a stream of N 2 gas [7] and the residue vortexed with 7 mg MBCD dissolved in 400 μl H 2 O. MDCK II cells were plated at 90% confluence and cultured for 72 h in DMEM/F-12, 5% delipidized BCS (98% CH -free), 1% P/S supplemented with a sufficient amount of photo-CH-MBCD complex to provide 50 μCi/ml [ 3 H]-photo-CH [7]. After rinsing in DPBS, 0.1 mM CaCl 2 , 1 mM MgCl 2 , 2% delipidized BCS, monolayers were irradiated in this solution for 1 h at RT, using a UV lamp placed 12 ins above the cells.…”

Section: Photoaffinity Lipid Labeling Experimentsmentioning

confidence: 99%

“…The role of membrane lipids in segregating the various TJ proteins into these substructures, however, is not known. Since occludin and the claudins are oligomerized, tetra-span integral membrane proteins [6], it is reasonable to expect that lipids in the bilayer might play an important role in their assembly and organization into functional TJ stands [7].…”

Section: Introductionmentioning

confidence: 99%

Cholesterol depletion alters detergent-specific solubility profiles of selected tight junction proteins and the phosphorylation of occludin

Lynch

Francis

McCarthy

et al. 2007

Experimental Cell Research

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Differential centrifugation of Triton X-100 or CHAPS lysates from control and cholesterol (CH) depleted MDCK II cells, segregated integral tight junction (TJ) proteins associated with detergent resistant membranes (DRMs) into two groups. Group A proteins (occludin, claudin-2 and -3) were detected in large, intermediate and small aggregates in both detergents, whereas group B proteins (claudin-1, -4 and -7) were observed in small aggregates in TX-100 and in intermediate and small aggregates in CHAPS. Depletion of CH altered the distribution of group A and B proteins among the three size categories in a detergent-specific manner. In lysates produced with octyl glucoside, a detergent that selectively extracts proteins from DRMs, group A proteins were undetectable in large aggregates and CH depletion did not alter the distribution of either group A or B proteins in intermediate or small aggregates. Neither occludin (group A) nor claudin-1 (group B) was in intimate enough contact with CH to be cross-linked to [ 3 H]-photo-cholesterol. However, antibodies to either TJ protein co-immunoprecipitated caveolin-1, a CH-binding protein. Unlike claudins, occludin's presence in TJs and DRMs did not require palmitoylation. Equilibrium density centrifugation on discontinuous OptiPrep gradients revealed detergent-related differences in the densities of TJ-bearing DRMs. There was little or no change in those densities after CH depletion. Removing CH from the plasma membrane increased tyrosine and threonine phosphorylation of occludin, and transepithelial electrical resistance (TER) within 30 min. After 2 h of CH efflux, phospho-occludin levels and TER fell below control values. We conclude that the association of integral TJ proteins with DRMS, pelleted at low speeds, is partially CH dependent. However, the buoyant density of TJ-associated DRMs is a function of the detergent used and is insensitive to decreases in CH.

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“…It is a major structural component of plasma membranes and myelin, where it is critical for rapid conduction of nerve transmission. Cholesterol has also been directly implicated in various neuronal functions, including synaptogenesis and neurotransmitter release (Mauch et al, 2001 andThiele et al, 2000). Indirectly it has a general influence on cerebral biochemistry via conversion into bioactive steroids such as neurosteroids and oxysterols.…”

Section: Introductionmentioning

confidence: 99%

Bi-lateral changes to hippocampal cholesterol levels during epileptogenesis and in chronic epilepsy following focal-onset status epilepticus in mice

Heverin

Engel

Meaney³

et al. 2012

Brain Research

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Brain cholesterol homeostasis has been shown to be disrupted in neurodegenerative conditions such as Alzheimer's and Huntington's diseases. Investigations in animal models of seizure--induced brain injury suggest that brain cholesterol levels are altered by prolonged seizures (status epilepticus) and are a feature of the pathophysiology of temporal lobe epilepsy. The present study measured hippocampal sterol levels in a model of unilateral hippocampal injury triggered by focal--onset status epilepticus, and in chronically epileptic mice. Status epilepticus was induced by intra--amygdala microinjection of kainic acid and ipsilateral and contralateral hippocampus analyzed. No significant changes were found for ipsilateral or contralateral hippocampal levels of desmosterol or lathosterol at any time after SE as measured by gas chromatographymass spectrometry. 24S--hydroxycholesterol and cholesterol levels were unchanged up to 24 h after status epilepticus but were decreased in the ipsilateral hippocampus during early epileptogenesis and in chronically epileptic mice. Levels of cholesterol were also reduced in the contralateral hippocampus during epileptogenesis and in chronic epileptic mice. Treatment of mice with the anti--inflammatory cholesterol synthesis inhibitor lovastatin did not alter seizures during status epilepticus or seizure--induced neuronal death. Thus, changes to hippocampal cholesterol homeostasis predominantly begin during epileptogenesis, occur bi--laterally even when the initial precipitating injury is unilateral, and continue into the chronic epileptic period.

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Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles

Cited by 527 publications

References 47 publications

Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain

Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain

Cholesterol depletion alters detergent-specific solubility profiles of selected tight junction proteins and the phosphorylation of occludin

Bi-lateral changes to hippocampal cholesterol levels during epileptogenesis and in chronic epilepsy following focal-onset status epilepticus in mice

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