Lipids in biological membrane fusion

Chernomordik, Leonid V.; Kozlov, Michael M.; Zimmerberg, Joshua

doi:10.1007/bf00232676

Cited by 444 publications

(444 citation statements)

References 115 publications

Supporting

Mentioning

416

Contrasting

Unclassified

Order By: Relevance

“…These results (Figs. 3, 4, and 5) are consistent with a dual role for CHOL in the fusion mechanism: (1) a physiological fusion site/PFM organizer, defining fusion efficiency; and (2) a negative curvature-promoting FFM component, defining the ability to fuse [21,[25][26][27]72].…”

Section: Critical Roles For Chol In Triggered Membrane Fusionmentioning

confidence: 53%

A new approach to the molecular analysis of docking, priming, and regulated membrane fusion

Rogasevskaia

Coorssen

2011

J Chem Biol

View full text Add to dashboard Cite

Studies using isolated sea urchin cortical vesicles have proven invaluable in dissecting mechanisms of Ca 2+ -triggered membrane fusion. However, only acute molecular manipulations are possible in vitro. Here, using selective pharmacological manipulations of sea urchin eggs ex vivo, we test the hypothesis that specific lipidic components of the membrane matrix selectively affect defined late stages of exocytosis, particularly the Ca 2+ -triggered steps of fast membrane fusion. Egg treatments with cholesterol-lowering drugs resulted in the inhibition of vesicle fusion. Exogenous cholesterol recovered fusion extent and efficiency in cholesterol-depleted membranes; α-tocopherol, a structurally dissimilar curvature analogue, selectively restored fusion extent. Inhibition of phospholipase C reduced vesicle phosphatidylethanolamine and suppressed both the extent and kinetics of fusion. Although phosphatidylinositol-3-kinase inhibition altered levels of polyphosphoinositide species and reduced all fusion parameters, sequestering polyphosphoinositides selectively inhibited fusion kinetics. Thus, cholesterol and phosphatidylethanolamine play direct roles in the fusion pathway, contributing negative curvature. Cholesterol also organizes the physiological fusion site, defining fusion efficiency. A selective influence of phosphatidylethanolamine on fusion kinetics sheds light on the local microdomain structure at the site of docking/fusion. Polyphosphoinositides have modulatory upstream roles in priming: alterations in specific polyphosphoinositides likely represent the terminal priming steps defining fully docked, release-ready vesicles. Thus, this pharmacological approach has the potential to be a robust high-throughput platform to identify molecular components of the physiological fusion machine critical to docking, priming, and triggered fusion.

show abstract

Section: Critical Roles For Chol In Triggered Membrane Fusionmentioning

confidence: 53%

A new approach to the molecular analysis of docking, priming, and regulated membrane fusion

Rogasevskaia

Coorssen

2011

J Chem Biol

View full text Add to dashboard Cite

show abstract

“…Because of the relative size of the phospholipid head group, PA favors the formation of negative membrane curvature (concave), whereas PIP2 favors the generation of positive membrane curvature (convex). During the fusion reaction, PA is thought to stabilize and expand the outer membrane leaflets in the first transition from separated donor and acceptor bilayers to the hemifused state (fusion of the outer membrane bilayers only) (30,31). Similarly, the next transition between the hemifused state and full bilayer fusion requires that the inner bilayer half-membranes adopt a positive curvature; thus, this reaction intermediate favors the presence of phospholipids such as PIP2 (14).…”

Section: The Hemifusion Step Is the Rate-limiting Factor For In Vitromentioning

confidence: 99%

Asymmetric phospholipid distribution drives in vitro reconstituted SNARE-dependent membrane fusion

Vicogne

Vollenweider

Smith

et al. 2006

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

103

View full text Add to dashboard Cite

Insulin-stimulated glucose uptake requires the fusion of GLUT4 transporter-containing vesicles with the plasma membrane, a process that depends on the SNARE (soluble N-ethylmaleimide-sensitive fusion factor attachment receptor) proteins VAMP2 (vesicleassociated membrane protein 2) and syntaxin 4 (Stx4)͞SNAP23 (soluble N-ethylmaleimide-sensitive fusion factor attachment protein 23). Efficient SNARE-dependent fusion has been shown in many settings in vivo to require the generation of both phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). Addition of PA to Stx4͞SNAP23 vesicles markedly enhanced the fusion rate, whereas its addition to VAMP2 vesicles was inhibitory. In contrast, addition of PIP2 to Stx4͞SNAP23 vesicles inhibited the fusion reaction, and its addition to VAMP2 vesicles was stimulatory. The optimal distribution of phospholipids was found to trigger the progression from the hemifused state to full fusion. These findings reveal an unanticipated dependence of SNARE complex-mediated fusion on asymmetrically distributed acidic phospholipids and provide mechanistic insights into the roles of phospholipase D and PIP kinases in the late stages of regulated exocytosis.SNAP23 ͉ syntaxin 4 ͉ VAMP2

show abstract

“…Hemifusion must be initiated at a local site (Figure 11, local or restricted hemifusion), probably through the formation of a stalk (Chernomordik et al, 1995). The TM domains of the fusion proteins that buttress this structure could then physically destabilize the hemifusion diaphragm by a mechanism with little sequence requirement.…”

Section: The Wide Latitude In Functional Amino Acid Sequences In the mentioning

confidence: 99%

Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion

Melikyan

Lin

Roth

et al. 1999

MBoC

120

135

View full text Add to dashboard Cite

The amino acid sequence requirements of the transmembrane (TM) domain and cytoplasmic tail (CT) of the hemagglutinin (HA) of influenza virus in membrane fusion have been investigated. Fusion properties of wild-type HA were compared with those of chimeras consisting of the ectodomain of HA and the TM domain and/or CT of polyimmunoglobulin receptor, a nonviral integral membrane protein. The presence of a CT was not required for fusion. But when a TM domain and CT were present, fusion activity was greater when they were derived from the same protein than derived from different proteins. In fact, the chimera with a TM domain of HA and truncated CT of polyimmunoglobulin receptor did not support full fusion, indicating that the two regions are not functionally independent. Despite the fact that there is wide latitude in the sequence of the TM domain that supports fusion, a point mutation of a semiconserved residue within the TM domain of HA inhibited fusion. The ability of a foreign TM domain to support fusion contradicts the hypothesis that a pore is composed solely of fusion proteins and supports the theory that the TM domain creates fusion pores after a stage of hemifusion has been achieved. INTRODUCTIONMembrane fusion is common to many cellular processes, such as exocytosis and intracellular trafficking. But only in the case of viruses have the proteins responsible for fusion been unambiguously identified. A number of common features have been found among viral fusion proteins. All are oligomerized. The monomer of each oligomer always contains a critical stretch of nonpolar amino acids, known as the fusion peptide (Hernandez et al., 1996;Durell et al., 1997). As crystallographically determined, fusion proteins from several different virus families have the same backbone structure of extended coiled-coil ␣-helices (Bullough et al., 1994;Chan et al., 1997). Because viral fusion proteins of unrelated viruses have common structural patterns, it is logical to assume that their mechanisms of fusion are similar as well. Furthermore, a complex of SNARES, proteins thought to be responsible for the constitutive fusion of intracellular trafficking and the regulated fusion that occurs in exocytosis (Sü dhof, 1995), has been crystallographically determined (Poirier et al., 1998;Sutton et al., 1998). It too displays a long coiled-coil region. Therefore it may well be that the mechanisms of viral fusion pertain more generally to cellular fusion. Influenza virus has long been the prototypic virus for study of fusion mechanisms. It ‡ Corresponding author. E-mail address: fcohen@rush.edu. Abbreviations used: CF, carboxyfluorescein; CPZ, chlorpromazine; CT, cytoplasmic tail; DMEM, Dulbecco's modified Eagle's medium; GPI, glycosylphosphatidylinositol; HA, hemagglutinin; PBS-A-S, PBS supplemented with 0.1% sodium azide and 5% calf serum; p.i., postinfection; pIgR, polyimmunoglobulin receptor; R18, octadecylrhodamine B; RBC, red blood cell; RD, tetramethylrhodamine-tagged dextran; TM, transmembrane; VSV, vesicular stomatitis virus; WT,...

show abstract

Lipids in biological membrane fusion

Cited by 444 publications

References 115 publications

A new approach to the molecular analysis of docking, priming, and regulated membrane fusion

A new approach to the molecular analysis of docking, priming, and regulated membrane fusion

Asymmetric phospholipid distribution drives in vitro reconstituted SNARE-dependent membrane fusion

Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion

Contact Info

Product

Resources

About