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

• Published in: The Journal of cell biology Vol. 218; no. 10; pp. 3355 - 3371
• Main Authors: Miyagawa, Takuya, Hasegawa, Kana, Aoki, Yoko, Watanabe, Takuya, Otagiri, Yuka, Arasaki, Kohei, Wakana, Yuichi, Asano, Kenichi, Tanaka, Masato, Yamaguchi, Hideki, Tagaya, Mitsuo, Inoue, Hiroki
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 07.10.2019
• Subjects: Cell Membrane - metabolism; Cell surface; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endosomes; Golgi apparatus; Golgi Apparatus - metabolism; Humans; Invasiveness; Matrix metalloproteinase; Matrix Metalloproteinase 14 - metabolism; Matrix metalloproteinases; Membranes; Metalloproteinase; Metastases; Metastasis; Protein Transport; Qc-SNARE Proteins - metabolism; SNAP receptors; SNARE Proteins - metabolism; Syntaxin; Syntaxin 4; Transport; Tumor Cells, Cultured
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201808149

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.