Membrane lipids and vesicular traffic

Meer, Gerrit van; Sprong, Hein

doi:10.1016/j.ceb.2004.06.004

Cited by 159 publications

(45 citation statements)

References 50 publications

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“…S2C). The values we obtained are consistent with the low cholesterol and sphingolipid content of ER membranes 29 , 30 and with values obtained from synthetic bilayers mimicking the ER composition 31 , 32 . Furthermore, the bending rigidity of the ER membranes is similar to that of GUVs composed of pure PC, the major lipid of the ER, and significantly lower than that of artificial membranes containing cholesterol/sphingomyelin 1:1 or cholesterol/DOPC 1:1 lipid mixtures 5 …”

Section: Resultssupporting

confidence: 87%

An investigation of the effect of membrane curvature on transmembrane-domain dependent protein sorting in lipid bilayers

et al. 2014

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Sorting of membrane proteins within the secretory pathway of eukaryotic cells is a complex process involving discrete sorting signals as well as physico-chemical properties of the transmembrane domain (TMD). Previous work demonstrated that tail-anchored (TA) protein sorting at the interface between the Endoplasmic Reticulum (ER) and the Golgi complex is exquisitely dependent on the length and hydrophobicity of the transmembrane domain, and suggested that an imbalance between TMD length and bilayer thickness (hydrophobic mismatch) could drive long TMD-containing proteins into curved membrane domains, including ER exit sites, with consequent export of the mismatched protein out of the ER. Here, we tested a possible role of curvature in TMD-dependent sorting in a model system consisting of Giant Unilamellar Vesicles (GUVs) from which narrow membrane tubes were pulled by micromanipulation. Fluorescent TA proteins differing in TMD length were incorporated into GUVs of uniform lipid composition or made of total ER lipids, and TMD-dependent sorting and diffusion, as well as the bending rigidity of bilayers made of microsomal lipids, were investigated. Long and short TMD-containing constructs were inserted with similar orientation, diffused equally rapidly in GUVs and in tubes pulled from GUVs, and no difference in their final distribution between planar and curved regions was detected. These results indicate that curvature alone is not sufficient to drive TMD-dependent sorting at the ER-Golgi interface, and set the basis for the investigation of the additional factors that must be required.

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Section: Resultssupporting

confidence: 87%

An investigation of the effect of membrane curvature on transmembrane-domain dependent protein sorting in lipid bilayers

et al. 2014

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“…A sterol-rich membrane per se does not favor neurosteroid accumulation, because filipin labeling only partially overlapped that of KK-123 (Figure 1H). However, we hypothesize that the specific mixture of lipid components of the Golgi (Drin, 2014; van Meer and Sprong, 2004) is a determinant of the cellular distribution of neurosteroid analogues.…”

Section: Discussionmentioning

confidence: 98%

A clickable neurosteroid photolabel reveals selective Golgi compartmentalization with preferential impact on proximal inhibition

et al. 2016

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Anesthetic, GABA-active neurosteroids potently augment GABAA receptor function, leading to important behavioral consequences. Neurosteroids and their synthetic analogues are also models for a wide variety of cell-permeant neuroactive compounds. Cell permeation and compartmentalization raise the possibility that these compounds’ actions are influenced by their cellular partitioning, but these contributions are not typically considered experimentally or therapeutically. To examine the interplay between cellular accumulation and pharmacodynamics of neurosteroids, we synthesized a novel chemical biology analogue (bio-active, clickable photolabel) of GABA-active neurosteroids. We discovered that the analogue selectively photo-labels neuronal Golgi in rat hippocampal neurons. The active analogue’s selective distribution was distinct from endogenous cholesterol and not completely shared by some non-GABA active, neurosteroid-like analogues. On the other hand, the distribution was not enantioselective and did not require energy, in contrast to other recent precedents from the literature. We demonstrate that the soma-selective accumulation can act as a sink or source for steroid actions at plasma-membrane GABA receptors, altering steady-state and time course of effects at somatic GABAA receptors relative to dendritic receptors. Our results suggest a novel mechanism for compartment-selective drug actions at plasma-membrane receptors.

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“…Simons and Vaz [43] stated that, “rafts could be considered domains of a l o phase.” However, even though l o and l d phases are observed and measured in simple systems of model membranes, their concept cannot be directly applied to the living cell membranes. Nevertheless, it is likely that knowledge of how they form and their physico-chemical properties will contribute to our understanding of the formation mechanism, structure, lifetime, and dynamics of raft domains in biological membranes [67, 75, 78–83]. Results providing some insight into the structure and molecular interactions in l o and l d phases in PL bilayers are presented in Figs.…”

Section: Discussionmentioning

confidence: 99%

High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review

Subczynski

Pasenkiewicz-Gierula

Widomska

et al. 2017

Cell Biochem Biophys

230

160

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Lipid composition determines membrane properties, and cholesterol plays a major role in this determination as it regulates membrane fluidity and permeability as well as induces the formation of coexisting phases and domains in the membrane. Biological membranes display a very diverse lipid composition, the lateral organization of which plays a crucial role in regulating a variety of membrane functions. We hypothesize that, during biological evolution, membranes with a particular cholesterol content were selected to perform certain functions in the cells of eukaryotic organisms. In this review, we discuss the major membrane properties induced by cholesterol, and their relationship to certain membrane functions.

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Membrane lipids and vesicular traffic

Cited by 159 publications

References 50 publications

An investigation of the effect of membrane curvature on transmembrane-domain dependent protein sorting in lipid bilayers

An investigation of the effect of membrane curvature on transmembrane-domain dependent protein sorting in lipid bilayers

A clickable neurosteroid photolabel reveals selective Golgi compartmentalization with preferential impact on proximal inhibition

High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review

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