Intrinsically disordered region-mediated condensation of IFN-inducible SCOTIN/SHISA-5 inhibits ER-to-Golgi vesicle transport.

Newly synthesized proteins in the endoplasmic reticulum (ER) are sorted by coat protein complex II (COPII) at the ER exit site en route to the Golgi. Under cellular stresses, COPII proteins become targets of regulation to control the transport. Here, we show that the COPII outer coat proteins Sec31 and Sec13 are selectively sequestered into the biomolecular condensate of SCOTIN/SHISA-5, which interferes with COPII vesicle formation and inhibits ER-to-Golgi transport. SCOTIN is an ER transmembrane protein with a cytosolic intrinsically disordered region (IDR), which is required and essential for the formation of condensates. Upon IFN-γ stimulation, which is a cellular condition that induces SCOTIN expression and condensation, ER-to-Golgi transport was inhibited in a SCOTIN-dependent manner. Furthermore, cancer-associated mutations of SCOTIN perturb its ability to form condensates and control transport. Together, we propose that SCOTIN impedes the ER-to-Golgi transport through its ability to form biomolecular condensates at the ER membrane. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Nari Kim, Tae-Hyeon Kim, Chaelim Kim, Jee-Eun Lee, Myeong-Gyun Kang, Sanghee Shin, Minkyo Jung, Jong-Seo Kim, Ji Young Mun, Hyun-Woo Rhee, Seung-Yeol Park, Yongdae Shin, Joo-Yeon Yoo. Intrinsically disordered region-mediated condensation of IFN-inducible SCOTIN/SHISA-5 inhibits ER-to-Golgi vesicle transport. Developmental cell. 2023 Oct 09;58(19):1950-1966.e8

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PMID: 37816329

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