DRAM1 promotes the stability of lysosomal VAMP8 to enhance autolysosome formation and facilitates the extravasation

Rui Zhang, Xin Zhang, Hua Bai, Qiuyu Cheng, Xia Yao, Shi Li, Vincenzo Torraca, Chaojun Yan, Xueying Dong, Siyi Miao, Xueyuan Hu, Yeping Yu, Yueyan Wu, Hongfei Tan, Xin Chen, Shicheng Liu, Hao Lyu, Shuai Xiao, Dong Guo, Qi Zhang, Xing-Zhen Chen, Zhiyin Song (), Cefan Zhou () and Jingfeng Tang ()
Additional contact information
Rui Zhang: Hubei University of Technology
Xin Zhang: Hubei University of Technology
Hua Bai: Hubei University of Technology
Qiuyu Cheng: Hubei University of Technology
Xia Yao: Hubei University of Technology
Shi Li: Hubei University of Technology
Vincenzo Torraca: King’s College London
Chaojun Yan: Hubei University of Technology
Xueying Dong: Hubei University of Technology
Siyi Miao: Hubei University of Technology
Xueyuan Hu: Hubei University of Technology
Yeping Yu: Hubei University of Technology
Yueyan Wu: Hubei University of Technology
Hongfei Tan: Hubei University of Technology
Xin Chen: Hubei University of Technology
Shicheng Liu: Hubei University of Technology
Hao Lyu: Hubei University of Technology
Shuai Xiao: Hubei University of Technology
Dong Guo: Hubei University of Technology
Qi Zhang: Hubei University of Technology
Xing-Zhen Chen: University of Alberta
Zhiyin Song: Huazhong University of Science and Technology
Cefan Zhou: Hubei University of Technology
Jingfeng Tang: Hubei University of Technology

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: Abstract Autophagy classically functions to protect cells and organisms during stressful conditions by catabolizing intracellular components to maintain energy homeostasis. Lysosome-autophagosome fusion is a critical step in emptying degraded unwanted contents. However, the mechanism of autophagosome fusion with lysosomes is still not fully understood. Here, we report that DNA Damage-Regulated Autophagy Modulator 1 (DRAM1) interacts with Vesicle Associated Membrane Protein 8 (VAMP8) to mediate the fusion of autophagosomes with lysosomes. This DRAM1-VAMP8 interaction is enhanced upon stimulation of autophagy. However, DRAM1 preferentially mediates the fusion between autophagosomes and lysosomes by enhancing the assembly of the STX17-SNAP29-VAMP8 complex. Moreover, we reveal that DRAM1 specifically promotes the stability of lysosomal VAMP8 via inhibiting VAMP8 degradation by CHIP mediating ubiquitination. We also identify that DRAM1 inhibits the ubiquitination of VAMP8 at Lys 68,72, and 75 via competitively binding with CHIP. Furthermore, we demonstrate that DRAM1 promotes the extravasation of Hepatocellular Carcinoma (HCC) cells, and this process relies on enhanced autophagosome degradation. Our study reveals a mechanism for regulating autolysosome formation by DRAM1-VAMP8 association and suggests a potential strategy to inhibit the extravasation of HCC.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60887-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60887-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60887-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().