Fusion of Cells by Flipped SNAREs

  title={Fusion of Cells by Flipped SNAREs},
  author={Chuan Hu and Mahiuddin Ahmed and Thomas J. Melia and Thomas H. Söllner and Thomas Mayer and James E. Rothman},
  pages={1745 - 1749}
The SNARE (soluble N-ethylmaleimide–sensitive factor attachment protein receptor) hypothesis suggests that pairs of proteins known as vesicle (v-) SNAREs and target membrane (t-) SNAREs interact specifically to control and mediate intracellular membrane fusion events. Here, cells expressing the interacting domains of v- and t-SNAREs on the cell surface were found to fuse spontaneously, demonstrating that SNAREs are sufficient to fuse biological membranes. 

SNAREs and traffic.

  • W. Hong
  • Biology
    Biochimica et biophysica acta
  • 2005

Membrane traffic in the secretory pathway

SNARE (SNAP receptor) proteins drive intracellular membrane fusion and contribute specificity to membrane trafficking and the functional activity of some of these regulators determines the plasticity of regulated exocytosis.

A new catch in the SNARE.

Analysis of SNARE-mediated membrane fusion using an enzymatic cell fusion assay.

A new assay is described that quantifies SNARE-mediated cell fusion events by activated expression of β-galactosidase and offers a quantitative approach for analyzing SNARE -mediated membrane fusion and for high-throughput studies.

Selective Activation of Cognate SNAREpins by Sec1/Munc18 Proteins

Alternative Zippering as an On-Off Switch for SNARE-Mediated Fusion

Experiments are presented using a reconstituted fusion system that suggest a simple model in which the complexin accessory helix forms an alternative four-helix bundle with the target-SNARE near the membrane, preventing the vesicle- SNARE from completing its zippering.

A reduced SNARE model for membrane fusion.

A minimal model system was developed to mimic the SNARE-protein-mediated fusion of biological membranes and displays the key characteristics of in vivo fusion events.

Structure and function of SNARE and SNARE-interacting proteins

  • A. Brunger
  • Biology
    Quarterly Reviews of Biophysics
  • 2005
Physiological concentrations of neuronal SNAREs can juxtapose membranes, and promote fusion in vitro under certain conditions, however, significantly more work will be required to reconstitute an in vitro system that faithfully mimics the Ca2-triggered fusion of a synaptic vesicle at the active zone.

A common mechanism for the regulation of vesicular SNAREs on phospholipid membranes.

The data uncover a common mechanism for the control of SNARE engagement where intact phospholipid membranes rather than proteins down-regulate vesicular SNAREs in different cellular organelles.



Three SNARE complexes cooperate to mediate membrane fusion

  • Yuanyuan HuaR. Scheller
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
The increase in the inhibition of fusion observed with increasing concentration of inhibitor is best fit to a function that suggests three SNARE complexes cooperate to mediate fusion of a single vesicle.

Compartmental specificity of cellular membrane fusion encoded in SNARE proteins

It is found that, to a marked degree, the pattern of membrane flow in the cell is encoded and recapitulated by its isolated SNARE proteins, as predicted by the SNARE hypothesis.

Topological restriction of SNARE-dependent membrane fusion

Each SNARE protein is topologically restricted by design to function either as a v- SNARE or as part of a t-SNARE complex, and reconstituted two populations of phospholipid bilayer vesicles, with the individual SNARE proteins distributed in all possible combinations between them.

A t-SNARE of the endocytic pathway must be activated for fusion

It is shown that Tlg2p assembles with two light chains to form a functional t-SNARE that mediates fusion, specifically with the v- SNAREs Snc1p and Snc2p, which creates the potential for spatial and temporal regulation of fusion by signaling processes that unleash their fusion capacity.

SNAP receptors implicated in vesicle targeting and fusion

The existence of numerous SNARE-related proteins, each apparently specific for a single kind of vesicles or target membrane, indicates that NSF and SNAPs may be universal components of a vesicle fusion apparatus common to both constitutive and regulated fusion (including neurotransmitter release), in which the SNAREs may help to ensure vesICLE-to-target specificity.

Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

V0, the membrane-integral sector of the vacuolar H+-ATPase, is identified as a target of calmodulin on yeast vacuoles and radial expansion of such a protein pore may be a mechanism for intracellular membrane fusion.

Distinct SNARE complexes mediating membrane fusion in Golgi transport based on combinatorial specificity

It follows that the fusion potential and transport pathways of the yeast cell can be read out from its genome sequence according to the SNARE hypothesis with a predictive accuracy of about 99.6%.

Three-dimensional structure of the neuronal-Sec1–syntaxin 1a complex

The crystal structure of the nSec1–syntaxin 1a complex, determined at 2.6 Å resolution, reveals that major conformational rearrangements occur in syntaxin relative to both the core SNARE complex and isolated syntaxin.

Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins

Structurally targeted peptides are utilized to identify a “tC fusion switch” inherent to the coil domains of the neuronal t- SNARE that pairs with the cognate v-SNARE, implying that the intrinsically unstable coil in that region is a natural impediment to the completion of zippering, and thus, fusion.