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The exocyst is a Ral effector complex

Abstract

Delivery of cytoplasmic vesicles to discrete plasma-membrane domains is critical for establishing and maintaining cell polarity, neurite differentiation and regulated exocytosis. The exocyst is a multisubunit complex required for vectorial targeting of a subset of secretory vesicles. Mechanisms that regulate the activity of this complex in mammals are unknown. Here we show that Sec5, an integral component of the exocyst, is a direct target for activated Ral GTPases. Ral GTPases regulate targeting of basolateral proteins in epithelial cells, secretagogue-dependent exocytosis in neuroendocrine cells and assembly of exocyst complexes. These observations define Ral GTPases as critical regulators of vesicle trafficking.

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Figure 1: Effector-domain-dependent interaction of Ral GTPase with rSec5.
Figure 2: Ral signaling regulates basolateral membrane protein targeting.
Figure 3: RalA facilitates assembly of the exocyst complex.
Figure 4: RalA is required for appropriate basolateral membrane protein targeting.
Figure 5: Inhibition of Ral expression slows delivery of secretory vesicles to the plasma membrane.
Figure 6: Ral GTPases are activated in response to secretagogue, and modulate regulated secretion in PC12 cells.

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Acknowledgements

We thank Michael Roth, Karl Matlin, Ira Mellman, Alan Sorkin, Peter Novick and Philip Chavrier for some of the reagents used in these studies. We also thank Michael Roth for many helpful discussions and advice. This work was supported by the National Cancer Institute (CA71443), the Welch foundation (I-1414) and the Association de Recherche sur le Cancer (5440).

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Correspondence to Michael A. White.

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Moskalenko, S., Henry, D., Rosse, C. et al. The exocyst is a Ral effector complex. Nat Cell Biol 4, 66–72 (2002). https://doi.org/10.1038/ncb728

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