Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health - AgeCap, University of Gothenburg, 405 30, Gothenburg, Sweden.
Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan 9 C, 413 90, Gothenburg, Sweden.
Sci Rep. 2023 Aug 28;13(1):14068. doi: 10.1038/s41598-023-41188-0.
ER-to-Golgi trafficking partakes in the sorting of misfolded cytoplasmic proteins to reduce their cytological toxicity. We show here that yeast Sec7, a protein involved in proliferation of the Golgi, is part of this pathway and participates in an Hsp70-dependent formation of insoluble protein deposits (IPOD). Sec7 associates with the disaggregase Hsp104 during a mild heat shock and increases the rate of Hsp104 diffusion in an Hsp70-dependent manner when overproduced. Sec7 overproduction increased formation of IPODs from smaller aggregates and mitigated the toxicity of Huntingtin exon-1 upon heat stress while Sec7 depletion increased sensitivity to aẞ42 of the Alzheimer's disease and α-synuclein of the Parkinson's disease, suggesting a role of Sec7 in mitigating proteotoxicity.
内质网到高尔基体的运输参与了错误折叠细胞质蛋白的分拣，以降低其细胞毒性。我们在这里表明，酵母 Sec7 是一种参与高尔基体增殖的蛋白质，是该途径的一部分，并参与了 HSP70 依赖性不溶性蛋白沉积物（IPOD）的形成。Sec7 在轻度热激时与解聚酶 Hsp104 结合，并在过表达时以 HSP70 依赖的方式增加 Hsp104 的扩散速率。Sec7 的过表达增加了较小聚集体的 IPOD 形成，并减轻了热应激时 Huntingtin 外显子 1 的毒性，而 Sec7 的耗竭增加了对阿尔茨海默病的 Aβ42 和帕金森病的 α-突触核蛋白的敏感性，表明 Sec7 在减轻蛋白毒性方面的作用。
