Diacylglycerol-Rich Domain Formation in Giant Stearoyl-Oleoyl Phosphatidylcholine Vesicles Driven by Phospholipase C Activity

Riske, Karin A.; Döbereiner, Jürgen

doi:10.1016/s0006-3495(03)74659-1

Cited by 29 publications

(22 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the overall concentrations of DAG in many cell membranes are quite low, the local concentrations of DAG inside some membrane domains where DAGs are produced can be significantly higher [11][12][13]. Thus, the results from this study at 18.75% of DAG should be biologically relevant.…”

Section: Potential Mean Force (Pmf)mentioning

confidence: 68%

“…In cell membranes, the overall concentration of DAG is usually low, ranging from 1 to 8 mol% [7][8][9]. However, DAGs can be produced and accumulated in lipid domains [10]; thus the local concentration of DAG inside a membrane domain could be significantly higher [11][12][13]. DAGs can alter the intrinsic curvature of a membrane and facilitate phospholipase-C induced vesicle fusion [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alteration of lipid membrane structure and dynamics by diacylglycerols with unsaturated chains

Alwarawrah¹,

Hussain²,

Huang³

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

Diacylglycerols (DAGs) with unsaturated acyl chains play many important roles in biomembranes, such as a second messenger and activator for protein kinase C. In this study, three DAGs of distinctly different chain unsaturations (i.e. di16:0DAG (DPG), 16:0-18:1DAG (POG), and di18:1DAG (DOG)) are studied using atomistic MD simulation to compare their roles in the structure and dynamics of 16:0-18:1phosphatidylcholine (POPC) membranes. All three DAGs are able to produce the so-called 'condensing effect' in POPC membranes: decreasing area-per-lipid, and increasing acyl chain order and bilayer thickness. Our visual and quantitative analyses clearly show that DAG with unsaturated chains induce larger spacing between POPC headgroups, compared with DAG with saturated chains; this particular effect has long been hypothesized to be crucial for activating enzymes and receptors in cell membranes. DAGs with unsaturated chains are also located closer to the bilayer/aqueous interface than DPG and are more effective in slowing down lateral diffusion of molecules. We show that DAG molecules seek the "umbrella coverage" from neighboring phospholipid headgroups - similar to cholesterol. Unlike cholesterol, DAGs also hide their chains from water by laterally inserting their chains into the surrounding. Thus, acyl chains of DAG are more spread and disordered than those of PC due to the insertion. By calculating the potential of mean force (PMF) for POPC in POPC/DAG bilayers, we found that all three DAGs can significantly increase the free energy barrier for POPC to flip-flop, but only DAGs with unsaturated chains can additionally increase the free energy of POPC desorption.

show abstract

Section: Potential Mean Force (Pmf)mentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Alteration of lipid membrane structure and dynamics by diacylglycerols with unsaturated chains

Alwarawrah¹,

Hussain²,

Huang³

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

show abstract

“…The small-head group DAG molecule would result in increased membrane stress depicted in Fig. 4E as a deflection of the inner leaflet and increased curvature known to be a major determinant of stretch-activated channels (30)(31)(32)(33). This local curvature would cause increased stretch in the outer bilayer leaflet that would be akin to the effect of physical stretch applied to the whole bilayer.…”

Section: Resultsmentioning

confidence: 99%

A common mechanism underlies stretch activation and receptor activation of TRPC6 channels

Spassova

Hewavitharana

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

438

353

View full text Add to dashboard Cite

The TRP family of ion channels transduce an extensive range of chemical and physical signals. TRPC6 is a receptor-activated nonselective cation channel expressed widely in vascular smooth muscle and other cell types. We report here that TRPC6 is also a sensor of mechanically and osmotically induced membrane stretch. Pressure-induced activation of TRPC6 was independent of phospholipase C. The stretch responses were blocked by the tarantula peptide, GsMTx-4, known to specifically inhibit mechanosensitive channels by modifying the external lipid-channel boundary. The GsMTx-4 peptide also blocked the activation of TRPC6 channels by either receptor-induced PLC activation or by direct application of diacylglycerol. The effects of the peptide on both stretch-and diacylglycerol-mediated TRPC6 activation indicate that the mechanical and chemical lipid sensing by the channel has a common molecular mechanism that may involve lateral-lipid tension. The mechanosensing properties of TRPC6 channels highly expressed in smooth muscle cells are likely to play a key role in regulating myogenic tone in vascular tissue.GsMTx-4 peptide ͉ mechanosensitivity ͉ tarantula venom ͉ myogenic tone ͉ calcium signals T he superfamily of TRP cation channels transduce a remarkable spectrum of signals ranging from small secondmessenger molecules to physical parameters including temperature, osmolarity, and touch (1, 2). Among the several subfamilies of TRP channels, the TRPC nonselective cation channels activated in response to PLC-coupled receptors are widely expressed among tissues (2, 3). The closely related subgroup comprising TRPC3, TRPC6, and TRPC7 channels are directly activated by diacylglycerol through a PKC-independent mechanism (3, 4). TRPC6 channels are highly expressed in a number of different tissues including vascular smooth muscle cells (5-8). Despite their abundance, the exact physiological role of TRPC6 channels has not been elucidated. Recently it has been suggested that TRPC6 channels are involved in hemodynamic regulation (6, 9) and may play a role in generating myogenic tone in response to intravascular pressure in arteries (6, 9). This is a key mechanism to control blood flow in arteries and arterioles (10, 11) involving depolarization, activation of Ca 2ϩ entry, and the contraction of vascular smooth muscle cells (11). Increases in Ca 2ϩ in response to pressure not only activate smooth muscle cell contraction but also modify their growth and differentiation (12). However, the identity and gating mechanisms of the mechanical sensors that mediate the depolarizing response have not been identified.TRPC6 channels are expressed predominantly in cells responding to hydrostatic pressure changes including vascular smooth muscle and glomerular podocytes and have been implicated in mediating pressure-induced responses (6, 13). TRPC6 channels mediate receptor-induced depolarization in smooth muscle cells (7,9), and opening of the related TRPC1 channel has been shown to be activated by stretch (14). In addition to being implicated in ...

show abstract

“…In this paper we have reviewed work mainly done on vesicles in inert solutions or in the presence of amphiphiles. A large amount of research has also been done on vesicles in the presence of substances (reactants) which interact with the membrane and alter the membrane composition (one example is provided by enzymes; see Riske and Döbereiner (2003)). A simple way of studying such effects is by performing local injection of the reactant in the vicinity of a giant vesicle, or by exchanging the external solution of a vesicle by a slow flow of the reactant solution.…”

Section: Discussionmentioning

confidence: 99%

A practical guide to giant vesicles. Probing the membrane nanoregime via optical microscopy

Dimova

Aranda

Bezlyepkina

et al. 2006

J. Phys.: Condens. Matter

300

321

View full text Add to dashboard Cite

Research on giant vesicles is becoming increasingly popular. Giant vesicles provide model biomembrane systems for systematic measurements of mechanical and rheological properties of bilayers as a function of membrane composition and temperature, as well as hydrodynamic interactions. Membrane response to external factors (for example electric fields, ions and amphiphilic molecules) can be directly visualized under the microscope. In this paper we review our current understanding of lipid bilayers as obtained from studies on giant unilamellar vesicles. Because research on giant vesicles increasingly attracts the interest of scientists from various backgrounds, we also try to provide a concise introduction for newcomers in the field. Finally, we summarize some recent developments on curvature effects induced by polymers, domain formation in membranes and shape transitions induced by electric fields.

show abstract

Diacylglycerol-Rich Domain Formation in Giant Stearoyl-Oleoyl Phosphatidylcholine Vesicles Driven by Phospholipase C Activity

Cited by 29 publications

References 57 publications

Alteration of lipid membrane structure and dynamics by diacylglycerols with unsaturated chains

Alteration of lipid membrane structure and dynamics by diacylglycerols with unsaturated chains

A common mechanism underlies stretch activation and receptor activation of TRPC6 channels

A practical guide to giant vesicles. Probing the membrane nanoregime via optical microscopy

Contact Info

Product

Resources

About