Phospholipid asymmetry in large unilamellar vesicles induced by transmembrane pH gradients

Hope, Michael J.; Redelmeier, Thomas E.; Wong, Kim F.; Rodrigueza, Wendi V.; Cullis, Pieter R.

doi:10.1021/bi00436a009

Cited by 105 publications

(112 citation statements)

References 40 publications

(47 reference statements)

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“…The transbilayer distribution of phospholipids in large unilamellar vesicles is highly pH sensitive (Hope et al, 1989). And a redistribution of only a small fraction of phospholipids suffices to induce shape changes in giant liposomes (Farge and Devaux, 1992).…”

Section: Discussionmentioning

confidence: 99%

Role of the V-ATPase in Regulation of the Vacuolar Fission–Fusion Equilibrium

Baars

Petri

Peters

et al. 2007

MBoC

140

182

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Like numerous other eukaryotic organelles, the vacuole of the yeast Saccharomyces cerevisiae undergoes coordinated cycles of membrane fission and fusion in the course of the cell cycle and in adaptation to environmental conditions. Organelle fission and fusion processes must be balanced to ensure organelle integrity. Coordination of vacuole fission and fusion depends on the interactions of vacuolar SNARE proteins and the dynamin-like GTPase Vps1p. Here, we identify a novel factor that impinges on the fusion-fission equilibrium: the vacuolar H ؉ -ATPase (V-ATPase) performs two distinct roles in vacuole fission and fusion. Fusion requires the physical presence of the membrane sector of the vacuolar H ؉ -ATPase sector, but not its pump activity. Vacuole fission, in contrast, depends on proton translocation by the V-ATPase. Eliminating proton pumping by the V-ATPase either pharmacologically or by conditional or constitutive V-ATPase mutations blocked salt-induced vacuole fragmentation in vivo. In living cells, fission defects are epistatic to fusion defects. Therefore, mutants lacking the V-ATPase display large single vacuoles instead of multiple smaller vacuoles, the phenotype that is generally seen in mutants having defects only in vacuolar fusion. Its dual involvement in vacuole fission and fusion suggests the V-ATPase as a potential regulator of vacuolar morphology and membrane dynamics. INTRODUCTIONCellular compartments are very dynamic structures that adapt their shape, size, and number to cellular metabolism, differentiation state, and environmental conditions. Changes in mitochondrial shape during animal development (Chan, 2006), proliferation and degradation of peroxisomes in response to nutrient availability (Yan et al., 2005), and extensive fragmentation of the mammalian Golgi during mitosis (Shorter and Warren, 2002) are only a few examples highlighting organellar dynamics. Organelle homeostasis in the face of permanent membrane remodeling requires an equilibration and coordination of the fundamental processes of membrane fission and fusion.Important insights into membrane dynamics have come from studies of the vacuole of the budding yeast Saccharomyces cerevisiae. Vacuoles are highly dynamic structures that undergo regulated cycles of membrane fission and fusion in the course of the cell cycle and in adaptation to changing environmental conditions. When a yeast cell buds and initiates growth of a daughter cell, the vacuole pinches off vesicles that migrate into the growing daughter cell where they fuse to form the new vacuolar compartment (Weisman, 2003). Vacuolar rearrangements also occur when yeast cells are faced with nutrient limitation or osmotic stress. Exposure of yeast cells to hypertonic medium induces fragmentation of the vacuole into numerous small vacuolar vesicles, a process involving Fab1p-mediated phosphatidylinositol-3,5-bisphosphate synthesis (Efe et al., 2005). Conversely, in fast adaptation to hypotonic shock, vacuoles fuse to give rise to a more voluminous vacuole. These rapid change...

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Section: Discussionmentioning

confidence: 99%

Role of the V-ATPase in Regulation of the Vacuolar Fission–Fusion Equilibrium

Baars

Petri

Peters

et al. 2007

MBoC

140

182

View full text Add to dashboard Cite

show abstract

“…A fab1 null strain entirely devoid of PtdIns(3,5)P 2 displays a dramatically enlarged vacuole. In addition, fab1 mutants show a reduction of vacuolar acidification (Weisman, 2003), which plays crucial roles in vacuolar fission (Baars et al, 2007) and vacuolar membrane structure (Hope et al, 1989). In Arabidopsis, there are four genes encoding putative Fab1p homologs (Mueller-Roeber and Pical, 2002).…”

Section: Discussionmentioning

confidence: 99%

The Arabidopsis Phosphatidylinositol 3-Kinase Is Important for Pollen Development

et al. 2008

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Phosphatidylinositol 3-kinase has been reported to be important for normal plant growth. To characterize the role of the enzyme further, we attempted to isolate Arabidopsis (Arabidopsis thaliana) plants that do not express the gene, but we could not recover homozygous mutant plants. The progeny of VPS34/vps34 heterozygous plants, harboring a T-DNA insertion, showed a segregation ratio of 1:1:0 for wild-type, heterozygous, and homozygous mutant plants, indicating a gametophytic defect. Genetic transmission analysis showed that the abnormal segregation ratio was due to failure to transmit the mutant allele through the male gametophyte. Microscopic observation revealed that 2-fold higher proportions of pollen grains in heterozygous plants than wild-type plants were dead or showed reduced numbers of nuclei. Many mature pollen grains from the heterozygous plants contained large vacuoles even until the mature pollen stage, whereas pollen from wild-type plants contained many small vacuoles beginning from the vacuolated pollen stage, which indicated that vacuoles in many of the heterozygous mutant pollen did not undergo normal fission after the first mitotic division. Taken together, our results suggest that phosphatidylinositol 3-kinase is essential for vacuole reorganization and nuclear division during pollen development.

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“…In the current study, the surface charge on the liposome bilayers was created by the presence of the cationic lipid stearylamine since it is known to distribute uniformly within the hydrophobic pool of the liposome (31,32). The leakage of tenofovir from phospholipon 100H/cholesterol/stearylamine liposomes during dialysis at 37°C as a function of stearylamine percentage is shown in Fig.…”

Section: Release Studymentioning

confidence: 96%

Near-Infrared Investigations of Novel Anti-HIV Tenofovir Liposomes

Zidan

Spinks

Fortunak

et al. 2010

AAPS J

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Abstract. Near-infrared (NIR) approaches is considered one of the most well-studied process analyzers evolving from the process analytical technology initiatives. The objective of this study was to evaluate NIR spectroscopy and imaging to assess individual components within a novel tenofovir liposomal formulation. By varying stearylamine, as a positive charge imparting agent, five batches were prepared by the thin film method. Each formulation was characterized in terms of drug entrapment efficiency, release characteristics, particle sizing, and zeta potential. Drug excipients compatibility was tested using Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The obtained results showed an increase in drug entrapment and a slower drug release by increasing the incorporated percentage of stearylamine. The compatibility testing revealed a significant interaction between the drug and some of the investigated excipients. The developed NIR calibration model was able to assess drug, phospholipid, and stearylamine levels along the batches. The calibration and prediction plots were linear with correlation coefficients of more than 0.9. The root square standard errors of calibration and prediction did not attain 5% of the measured values confirming the accuracy of the model. In contrast, NIR spectral imaging was capable of clearly distinguishing the different batches, both qualitatively and quantitatively. A linear relationship was obtained correlating the actual drug entrapped and the predicted values obtained from the partial least squares images.

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Phospholipid asymmetry in large unilamellar vesicles induced by transmembrane pH gradients

Cited by 105 publications

References 40 publications

Role of the V-ATPase in Regulation of the Vacuolar Fission–Fusion Equilibrium

Role of the V-ATPase in Regulation of the Vacuolar Fission–Fusion Equilibrium

The Arabidopsis Phosphatidylinositol 3-Kinase Is Important for Pollen Development

Near-Infrared Investigations of Novel Anti-HIV Tenofovir Liposomes

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