The SNARE-associated protein Sft2 functions in Imh1-mediated SNARE recycling transport upon ER stress

• Published in: Molecular biology of the cell Vol. 34; no. 11; p. 1
• Main Authors: Lai, Chun-Chi, Chiu, Wan-Yun, Chen, Yan-Ting, Wu, Chia-Lu, Lee, Fang-Jen S.
• Format: Journal Article
• Language: English
• Published: American Society for Cell Biology 01.10.2023; The American Society for Cell Biology
• Subjects: Biological transport; Cell research; Endoplasmic reticulum; Membrane proteins; Physiological aspects; Taiwan
• ISSN: 1059-1524; 1939-4586; 1939-4586
• DOI: 10.1091/mbc.E23-01-0019

Vesicular trafficking involving SNARE proteins play a crucial role in the delivery of cargo to the target membrane. Arf-like protein 1 (Arl1) is an important regulator of the endosomal trans-Golgi network (TGN) and secretory trafficking. In yeast, ER stress-enhances Arl1 activation and Golgin Imh1 recruitment to the late-Golgi. Although Arl1 and Imh1 are critical for GARP-mediated endosomal SNARE-recycling transport in response to ER stress, their downstream effectors are unknown. Here, we report that the SNARE-associated protein Sft2 acts downstream of the Arl1–Imh1 axis to regulate SNARE recycling upon ER stress. We first demonstrated that Sft2 is required for Tlg1/Snc1 SNARE-recycling transport under tunicamycin-induced ER stress. Interestingly, we found that Imh1 regulates Tlg2 retrograde transport to the late-Golgi under ER stress, which in turn is required for Sft2 targeting to the late-Golgi. We further showed that Sft2 with 40 amino acids deleted from the N-terminus exhibits defective mediation of SNARE recycling and decreased association with Tlg1 under ER stress. Finally, we demonstrated that Sft2 is required for GARP-dependent endosome-to-Golgi transport in the absence of Rab protein Ypt6. This study highlights Sft2 as a critical downstream effector of the Arl1-Imh1 axis, mediating the endosome-to-Golgi transport of SNAREs.