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Actin and Arf1-dependent recruitment of a cortactin–dynamin complex to the Golgi regulates post-Golgi transport

Nature Cell Biology volume 7, pages 483–492 (2005)Cite this article

Abstract

Cortactin is an actin-binding protein that has recently been implicated in endocytosis. It binds directly to dynamin-2 (Dyn2), a large GTPase that mediates the formation of vesicles from the plasma membrane and the Golgi. Here we show that cortactin associates with the Golgi to regulate the actin- and Dyn2-dependent transport of cargo. Cortactin antibodies stain the Golgi apparatus, labelling peripheral buds and vesicles that are associated with the cisternae. Notably, in vitro or intact-cell experiments show that activation of Arf1 mediates the recruitment of actin, cortactin and Dyn2 to Golgi membranes. Furthermore, selective disruption of the cortactin–Dyn2 interaction significantly reduces the levels of Dyn2 at the Golgi and blocks the transit of nascent proteins from the trans-Golgi network, resulting in swollen and distended cisternae. These findings support the idea of an Arf1-activated recruitment of an actin, cortactin and Dyn2 complex that is essential for Golgi function.

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Figure 1: Immunofluorescence staining of cultured epithelial cells reveals a localization of cortactin to the Golgi.
Figure 2: Cortactin is in intimate contact with Golgi-associated buds and vesicles.
Figure 3: Binding of cortactin and dynamin to isolated Golgi membranes is dependent upon Arf1-activated actin recruitment.
Figure 4: Disruption of cortactin function reduces Dyn2 recruitment to the Golgi apparatus.
Figure 5: VSV-G-ts–GFP that is transported from the ER accumulates in the Golgi of cells expressing truncated cortactin proteins.
Figure 6: BHK-21 cells expressing CortΔSH3 accumulate large amounts of nascent VSV-G protein and show large, distended Golgi cisternae.
Figure 7: Expression of truncated cortactin and dynamin blocks the movement of VSV-G protein from the TGN to the cell surface.

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Acknowledgements

This work was supported by a grant from the National Institutes of Health (DK56647) to M.A.M.

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Author notes

  1. Hong Cao and Shaun Weller: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Basic Research in Digestive Diseases and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, 55905, Minnesota, USA

    Hong Cao, Shaun Weller, Jing Chen, Bing Huang & Mark A. McNiven

  2. Department of Biochemistry and Molecular Biology, 1642D Guggenheim Building, Mayo Clinic, 200 First Street SW, Rochester, 55905, MN, USA

    James D. Orth & Mark A. McNiven

  3. Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, 52242, Iowa, USA

    Ji-Long Chen & Mark Stamnes

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Correspondence to Mark A. McNiven.

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Cao, H., Weller, S., Orth, J. et al. Actin and Arf1-dependent recruitment of a cortactin–dynamin complex to the Golgi regulates post-Golgi transport. Nat Cell Biol 7, 483–492 (2005). https://doi.org/10.1038/ncb1246

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