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CELLULAR TRAFFICKING

Rendezvous of Retro-2 at the ER

Nature Chemical Biology volume 16, pages 229–230 (2020)Cite this article

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Retro-2 is a drug that protects cells against bacterial and plant toxins by arresting their trafficking in endosomes. New data show that the target for Retro-2 is surprisingly not within the endosomal system, but on the endoplasmic reticulum.

Many bacterial and plant toxins undertake a journey that starts from the plasma membrane, goes over several endomembrane organelles and finally reaches the endoplasmic reticulum (ER). For instance, the Shiga toxin and Shiga-like toxins (SLT), once internalized, travel from early endosomes toward the Golgi and then traffic back to the ER. Various factors have been identified to mediate the transit of Shiga toxin from the endosome to the ER. For example, GPP130 is a manganese-sensitive membrane protein known to be involved in the trafficking of Shiga toxins from endosomes to the Golgi1. Understanding the various retrograde trafficking pathways may enable the identification of novel drug targets. The small molecule Retro-2 is known to block SLT trafficking between the endosomes and the Golgi. Although the target of Retro-2 was predicted to be in the endosomal system, the mechanism of action remained elusive. In this issue, Forrester and colleagues2 identified the target of Retro-2 as Sec16A, a protein known to act as a scaffold that organizes ER exit sites (ERES).

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Fig. 1: The newly identified mode of action of Retro2.

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  1. Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, Oslo, Norway

    Hesso Farhan

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  1. Hesso Farhan
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Correspondence to Hesso Farhan.

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The author declares no competing interests.

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Farhan, H. Rendezvous of Retro-2 at the ER. Nat Chem Biol 16, 229–230 (2020). https://doi.org/10.1038/s41589-020-0475-3

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  • DOI: https://doi.org/10.1038/s41589-020-0475-3

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