Abstract
The Ras-related small GTPase RalA is involved in controlling actin cytoskeletal remodelling and vesicle transport in mammalian cells1,2. We identified the mammalian homologue of Sec5, a subunit of the exocyst complex determining yeast cell polarity, as a specific binding partner for GTP-ligated RalA. Inhibition of RalA binding to Sec5 prevents filopod production by tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) and by activated forms of RalA and Cdc42, signalling intermediates downstream of these inflammatory cytokines. We propose that the RalA–exocyst complex interaction integrates the secretory and cytoskeletal pathways.
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Acknowledgements
We thank T. Stossel and J. Hartwig for critical reading of the manuscript. This work was supported by Grant HL19429 from the United States Public Health Service and by the Edwin S. Webster Foundation.
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Supplementary Figures and Tables
Table S1 MALDI-TOF/MS analysis of p85, p108, and p110 peptides. (PDF 300 kb)
Figure S1 Mapping of the RalA binding domain of Sec5.
Figure S2 Specificity of the anti-Sec5 antibody
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Sugihara, K., Asano, S., Tanaka, K. et al. The exocyst complex binds the small GTPase RalA to mediate filopodia formation. Nat Cell Biol 4, 73–78 (2002). https://doi.org/10.1038/ncb720
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DOI: https://doi.org/10.1038/ncb720
