MT1-MMP recruits the ER-Golgi SNARE Bet1 for efficient MT1-MMP transport to the plasma membrane.

Abstract

Metastasis is a major cause of cancer-related death. Membrane type 1-matrix metalloproteinase (MT1-MMP) is a critical protease for local invasion and metastasis. MT1-MMP is synthesized in the endoplasmic reticulum (ER) and transported in vesicles to invadopodia, specialized subdomains of the plasma membrane, through secretory and endocytic recycling pathways. The molecular mechanism underlying intracellular transport of MT1-MMP has been extensively studied, but is not fully understood. We show that MT1-MMP diverts the SNARE Bet1 from its function in ER-Golgi transport, to promote MT1-MMP trafficking to the cell surface, likely to invadopodia. In invasive cells, Bet1 is localized in MT1-MMP-positive endosomes in addition to the Golgi apparatus, and forms a novel SNARE complex with syntaxin 4 and endosomal SNAREs. MT1-MMP may also use Bet1 for its export from raft-like structures in the ER. Our results suggest the recruitment of Bet1 at an early stage after MT1-MMP expression promotes the exit of MT1-MMP from the ER and its efficient transport to invadopodia.

• Authors: Takuya Miyagawa, Kana Hasegawa, Yoko Aoki, Takuya Watanabe, Yuka Otagiri, Kohei Arasaki, Yuichi Wakana, Kenichi Asano, Masato Tanaka, Hideki Yamaguchi, Mitsuo Tagaya, Hiroki Inoue
• Journal: The Journal of cell biology (J Cell Biol) Vol. 218 Issue 10 Pg. 3355-3371 (10 07 2019) ISSN: 1540-8140 [Electronic] United States
• PMID: 31519727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Miyagawa et al.

Chemical References

• BET1L protein, human
• Qc-SNARE Proteins
• SNARE Proteins
• MMP14 protein, human
• Matrix Metalloproteinase 14

Topics

• Cell Membrane (metabolism)
• Endoplasmic Reticulum (metabolism)
• Golgi Apparatus (metabolism)
• Humans
• Matrix Metalloproteinase 14 (metabolism)
• Protein Transport
• Qc-SNARE Proteins (metabolism)
• SNARE Proteins (metabolism)
• Tumor Cells, Cultured