Potential ER tubular lumen sensing by intrinsically disordered regions

Intrinsically disordered regions (IDRs) are known to sense the positive membrane curvature of vesicles and tubules. However, whether IDRs can sense the negative curvature of their luminal surfaces remains elusive. Here, we show that IDRs direct specific localization to endoplasmic reticulum (ER) tubules. In Saccharomyces cerevisiae, Sed4 interacts with Sec16 at the ER exit site (ERES) to promote ER export. Upon loss of this interaction, Sed4 failed to assemble at the ERES but was enriched in the ER tubules in a luminal region-dependent manner. Fusion of the Sed4 luminal region with Sec12 and Sec22, which localize throughout the ER, resulted in their enrichment in the tubules. The luminal regions of Sed4 or its homologs, predicted to be IDRs, localized to tubules when translocated alone into the ER lumen. The lumen-imported IDRs derived from cytosol-localizing Sec16 and Atg13 also exhibited tubule localization. Furthermore, Sed4 constructs in which the luminal region was replaced by these IDRs were concentrated at the ERES. Collectively, we suggest that the IDRs sense the properties of the tubule lumen, such as its surface, and facilitate Sed4 assembly at the ERES.