Sec61β facilitates the maintenance of endoplasmic reticulum homeostasis by associating microtubules

Sec61 beta, a subunit of the Sec61 translocon complex, is not essential in yeast and commonly used as a marker of endoplasmic reticulum (ER). In higher eukaryotes, such as Drosophila, deletion of Sec61 beta causes lethality, but its physiological role is unclear. Here, we show that Sec61 beta interacts directly with microtubules. Overexpression of Sec61 beta containing small epitope tags, but not a RFP tag, induces dramatic bundling of the ER and microtubule. A basic region in the cytosolic domain of Sec61 beta is critical for microtubule association. Depletion of Sec61 beta induces ER stress in both mammalian cells and Caenorhabditis elegans, and subsequent restoration of ER homeostasis correlates with the microtubule binding ability of Sec61 beta. Loss of Sec61 beta causes increased mobility of translocon complexes and reduced level of membrane-bound ribosomes. These results suggest that Sec61 beta may stabilize protein translocation by linking translocon complex to microtubule and provide insight into the physiological function of ER-microtubule interaction.