Parchure Anup, Tejada Helen, Xi Zhiqun, Kim Yeongho, Su Maohan, Yan You, Julca-Zevallos Omar, Alcázar-Román Abel R, Villemeur Marie, Liu Xinran, Toomre Derek, Raote Ishier, Bogan Jonathan S
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
Nat Commun. 2025 Jul 1;16(1):5518. doi: 10.1038/s41467-025-60691-8.
The Endoplasmic Reticulum (ER)-Golgi Intermediate Compartment (ERGIC) is a network of tubules and vesicles known for producing COPI vesicles and receiving COPII vesicles from the ER. Much about its identity, stability, and regulation remains unknown. Here, we show that TUG (UBXN9, Aspscr1) protein, a central regulator of GLUT4 trafficking, localizes to the ERGIC, and that its deletion enhances anterograde flux of a model soluble cargo protein. TUG deletion redistributes ERGIC markers to the cis-Golgi and alters Golgi morphology. TUG forms biomolecular condensates in vitro and contains a central disordered region that mediates its recruitment to ERGIC membranes. A distinct N-terminal region mediates its oligomerization in cells. TUG deletion disrupts ERGIC-dependent processes, including autophagy and collagen secretion, and alters the targeting of the CFTR chloride channel. We conclude that TUG organizes and stabilizes ERGIC membranes to support their roles in diverse secretory and degradative membrane trafficking pathways.
内质网-高尔基体中间区室（ERGIC）是一个由小管和囊泡组成的网络，以产生COPI囊泡并接收来自内质网的COPII囊泡而闻名。关于它的身份、稳定性和调节，仍有许多未知之处。在这里，我们表明，TUG（UBXN9，Aspscr1）蛋白是GLUT4转运的核心调节因子，定位于ERGIC，并且其缺失增强了模型可溶性货物蛋白的顺向通量。TUG缺失将ERGIC标志物重新分布到顺面高尔基体并改变高尔基体形态。TUG在体外形成生物分子凝聚物，并包含一个中央无序区域，该区域介导其被招募到ERGIC膜上。一个独特的N端区域介导其在细胞中的寡聚化。TUG缺失破坏了依赖ERGIC的过程，包括自噬和胶原蛋白分泌，并改变了CFTR氯离子通道的靶向。我们得出结论，TUG组织并稳定ERGIC膜，以支持它们在多种分泌和降解性膜运输途径中的作用。
