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Discs-Large and Strabismus are functionally linked to plasma membrane formation

Nature Cell Biology volume 5, pages 987–993 (2003)Cite this article

Abstract

During early embryogenesis in Drosophila melanogaster, extensive vesicle transport occurs to build cell boundaries for 6,000 nuclei. Here we show that this important process depends on a functional complex formed between the tumour suppressor and adaptor protein Discs-Large (Dlg)1 and the integral membrane protein Strabismus (Stbm)/Van Gogh (Vang)2,3. In support of this idea, embryos with mutations in either dlg or stbm displayed severe defects in plasma membrane formation. Conversely, overexpression of Dlg and Stbm synergistically induced excessive plasma membrane formation. In addition, ectopic co-expression of Stbm (which associated with post-Golgi vesicles) and the mammalian Dlg homologue SAP97/hDlg4,5 promoted translocation of SAP97 from the cytoplasm to both post-Golgi vesicles and the plasma membrane. This effect was dependent on the interaction between Stbm and SAP97. These findings suggest that the Dlg–Stbm complex recruits membrane-associated proteins and lipids from internal membranes to sites of new plasma membrane formation.

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Figure 1: Dlg interacts with Stbm.
Figure 2: Epithelial cells of stbm mutant embryos exhibit defects in membrane formation.
Figure 3: Expression pattern of Stbm and Dlg in fly and mammalian cells.
Figure 4: Dlg and Stbm must interact to colocalize and promote membrane formation.
Figure 5: Dlg is required for plasma membrane formation in both embryos and larvae.

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Acknowledgements

We thank M. Kuroda, R. Kelley, S. Izaddoost, and K.-W. Choi for valuable discussions, T. Wolff for stbm mutants and stbm cDNA, P. Bryant for dlg mutants and guinea pig anti-Dlg antibody, S. Ou and P. Patterson for generating anti-Stbm antibody, M. Lowe for anti-GM130 antibody, S. Elledge for two-hybrid system reagents, H. Bellen for Hrs and Nrx antibodies, and the Bloomington Stock Center for fly strains. K.K.F. was the recipient of the Viral Oncology Training Grant predoctoral fellowship T32 CA009197. R.T.J. and K.-O.C. were supported by National Institutes of Health grants RO1 CA058541 and R29 NS35532, respectively.

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  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, TX, USA

    Ok-Kyung Lee, Jennifer S. James, Darshana Chadda, Zhi-Hong Chen & Kyung-Ok Cho

  2. Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, TX, USA

    Kristopher K. Frese & Ronald T. Javier

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Lee, OK., Frese, K., James, J. et al. Discs-Large and Strabismus are functionally linked to plasma membrane formation. Nat Cell Biol 5, 987–993 (2003). https://doi.org/10.1038/ncb1055

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