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Compartmental specificity of cellular membrane fusion encoded in SNARE proteins

Nature volume 407, pages 153–159 (2000)Cite this article

Abstract

Membrane-enveloped vesicles travel among the compartments of the cytoplasm of eukaryotic cells, delivering their specific cargo to programmed locations by membrane fusion. The pairing of vesicle v-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) with target membrane t-SNAREs has a central role in intracellular membrane fusion. We have tested all of the potential v-SNAREs encoded in the yeast genome for their capacity to trigger fusion by partnering with t-SNAREs that mark the Golgi, the vacuole and the plasma membrane. Here we find 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.

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Figure 1: Characterization of liposomes.
Figure 2: The yeast exocytic SNAREs can fuse vesicles.
Figure 3: Compartmental specificity is determined by SNARE interactions.
Figure 4: Specificity of the three functional t-SNARE complexes versus all other potential v-SNAREs.
Figure 5: Ykt6 anchored with a short-chain isoprenoid does not fuse.

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Acknowledgements

We wish to thank Dr Paul A. Marks for two decades of exemplary leadership of Memorial Sloan-Kettering Cancer Center and for creating the environment that made possible the discovery of SNARE proteins and their role in cell biology. We also thank L. Katz and P. Brennwald for plasmids, B. Brügger for help in the construction of the TLG1 clone, and T. Melia for cryo-electron microscopy of liposomes. Research was supported by an NIH grant (to J.E.R.) and postdoctoral fellowships of the Medical Research Council of Canada (F.P.), the NIH (J.M.), and the Japanese Society for the Promotion of Science (R.F.).

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Author notes

  1. James A. McNew

    Present address: Department of Biochemistry and Cell Biology, Rice University, MS140, 6100 Main Street, PO Box 1892, Houston, Texas, 77251-1892, USA

  2. Ryouichi Fukuda

    Present address: Department of Biotechnology, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan

  3. Francesco Parlati and Ryouichi Fukuda: These authors contributed equally to this work

  4. Correspondence and requests for materials should be addressed to J.E.R. .

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    1. James A. McNew
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    Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 251, New York, New York 10021, USA

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    McNew, J., Parlati, F., Fukuda, R. et al. Compartmental specificity of cellular membrane fusion encoded in SNARE proteins. Nature 407, 153–159 (2000). https://doi.org/10.1038/35025000

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