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SNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P

Nature Cell Biology volume 3, pages 658–666 (2001)Cite this article

Abstract

The sorting nexin (SNX) protein family is implicated in regulating membrane traffic, but the mechanism is still unknown. We show that SNX3 is associated with the early endosome through a novel motif (PX domain) capable of interaction with phosphatidylinositol-3-phosphate (PtdIns(3)P). Overexpression of SNX3 alters endosomal morphology and delays transport to the lysosome. Transport from the early to the recycling endosome is affected upon microinjection of SNX3 antibodies. Our results highlight a novel mechanism by which SNX proteins regulate traffic and uncover a novel class of effectors for PtdIns(3)P.

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Figure 1: SNX3 is enriched in the early endosome.
Figure 2: SNX3 localizes together with internalized anti-TfR antibody on its way to the recycling endosome.
Figure 3: Preferential association of SNX3 with tubular–vesicular structures and tubular extensions of the early endosome.
Figure 4: Wortmannin-sensitive endosomal association of SNX3.
Figure 5: PX-domain-dependent direct interaction of SNX3 with PtdIns(3)P.
Figure 6: Overexpression of SNX3 results in alterations of endosomal morphology.
Figure 7: SNX3 overexpression causes the formation of expanded tubular–vesicular structures.
Figure 8: SNX3 regulates endosomal traffic.
Figure 9: SNX3 mutants defective in interaction with PtdIns(3)P fail to associate with the endosome and to affect the endosomal pathway.

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Acknowledgements

We thank K. von Figura for antibodies against the Mr 46K M6PR, B. L. Tang and P. Singh for critical reading of the manuscript, D. E. James for insightful discussions, and Y. H. Tan for his continuous support. This work was funded by the Institute of Molecular and Cell Biology (to W.H.).

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  1. Membrane Biology Laboratory, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore, 117609, Singapore

    Yue Xu, Heinz Hortsman, Lifong Seet, Siew Heng Wong & Wanjin Hong

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Correspondence to Wanjin Hong.

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Xu, Y., Hortsman, H., Seet, L. et al. SNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P. Nat Cell Biol 3, 658–666 (2001). https://doi.org/10.1038/35083051

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