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Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network

Nature Cell Biology volume 6, pages 106–112 (2004)Cite this article

Abstract

Protein kinase D (PKD) binds to diacylglycerol (DAG) in the trans-Golgi network (TGN) and is activated by trimeric G-protein subunits βγ. This complex then regulates the formation of transport carriers in the TGN that traffic to the plasma membrane in non-polarized cells. Here we report specificity of different PKD isoforms in regulating protein trafficking from the TGN. Kinase-inactive forms of PKD1, PKD2 and PKD3 localize to the TGN in polarized and non-polarized cells. PKD activity is required only for the transport of proteins containing basolateral sorting information, and seems to be cargo specific.

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Figure 1: PKD2-KD localized to the TGN causes extensive tubulation and blocks transport to the cell surface.
Figure 2: KD isoforms of PKD localize to the TGN of MDCK cells.
Figure 3: Expression of mutant PKD1 or PKD2 does not affect transport to the apical domain in polarized MDCK cells.
Figure 4: Expression of mutant PKD1 or PKD2 blocks transport to the basolateral surface.
Figure 5: Non-polarized HeLa cells sort proteins into apical-like (PKD-independent) and basolateral-like (PKD-dependent) pathways.

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Acknowledgements

Work in the Malhotra laboratory is funded by grants (GM 53747 and GM 46224) from the NIH and the Human Frontier Science Program, in the Nelson laboratory from the NIH (GM35227), and by a Howard Hughes Medical Institute Biomedical Research Support Program Faculty Startup Package to C.Y. I.A. is supported by a fellowship from the Spanish Ministry of Education, Culture and Sport.

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Author notes

  1. Charles Yeaman, M. Inmaculada Ayala and Vivek Malhotra: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Iowa, Iowa City, 52242-1109, IA, USA

    Charles Yeaman

  2. Cell and Developmental Biology, University of California San Diego, La Jolla, 92093-0347, CA, USA

    M. Inmaculada Ayala, Frederic Bard, Carine Bossard & Vivek Malhotra

  3. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, 94305-5345, CA, USA

    Charles Yeaman, Jessica R. Wright & W. James Nelson

  4. Department of Cell Biology, Yale University, New Haven, 06520-8002, CT, USA

    Agnes Ang & Ira Mellman

  5. Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan

    Yusuke Maeda

  6. Department of Internal Medicine I, University of Ulm, Ulm, 89071, Germany

    Thomas Seufferlein

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Correspondence to Vivek Malhotra.

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Yeaman, C., Ayala, M., Wright, J. et al. Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network. Nat Cell Biol 6, 106–112 (2004). https://doi.org/10.1038/ncb1090

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