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p47 is a cofactor for p97-mediated membrane fusion

Nature volume 388, pages 75–78 (1997)Cite this article

Abstract

At least two distinct ATPases, NSF and p97, are known to be involved in the heterotypic fusion of transport vesicles with their target membranes and the homotypic fusion of membrane compartments1. The NSF-mediated fusion pathway is the best characterized, many of the components having been identified and their functions analysed2,3,4,5,6,7. In contrast, none of the accessory proteins for the p97-mediated fusion pathway has been identified8,9,10. Now we have identified the first such component, a protein of relative molecular mass 47,000 (p47), which forms a tight, stoichiometric complex with cytosolic p97 (one trimer of p47 per hexamer of p97). It is essential for the p97-mediated regrowth of Golgi cisternae from mitotic Golgi fragments, a process restricted to animal cells11. As a homologue of p47 exists in budding yeast, this indicates that it might also be involved in other membrane fusion reactions catalysed by p97, such as karyogamy10.

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Figure 1: Gel filtration of p47 and p97.
Figure 2: Association of p47 with p97.
Figure 3: Predicted sequence of p47 and the yeast homologue Shp1.
Figure 4: Negative staining of pure p97 and the p97/p47 complex.
Figure 5: Effect of p47 on p97-mediated cisternal regrowth from mitotic Golgi fragments.

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Acknowledgements

We thank T. Chappell, F. Barr, B. Svejstrup, B. Sönnichsen, M. Lowe, C. Fernandez, D. Shima, J. Shorter, N. Hui and A. Coffer for helpful comments and for reagents; G. Banting for the rat liver cDNA library; J.-M. Peters for monoclonal anti-p97 antibodies; G. Clark and A. Davies for DNA sequencing; and D. Rahman for protein sequencing. Special thanks go to N. Nakamura for advice.

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Authors and Affiliations

  1. *Cell Biology Laboratory Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Hisao Kondo, Catherine Rabouille & Graham Warren

  2. †Protein Structure Laboratory Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Richard Newman & Paul Freemont

  3. §Protein Sequencing Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Darryl Pappin

  4. ‡MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    Timothy P. Levine

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  1. Hisao Kondo
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Correspondence to Graham Warren.

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Kondo, H., Rabouille, C., Newman, R. et al. p47 is a cofactor for p97-mediated membrane fusion. Nature 388, 75–78 (1997). https://doi.org/10.1038/40411

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