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Domain architecture of vasohibins required for their chaperone‐dependent unconventional extracellular release
Author(s) -
Kadonosono Tetsuya,
Yimchuen Wanaporn,
Tsubaki Takuya,
Shiozawa Tadashi,
Suzuki Yasuhiro,
Kuchimaru Takahiro,
Sato Yasufumi,
KizakaKondoh Shinae
Publication year - 2017
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3089
Subject(s) - extracellular , cytosol , secretion , microbiology and biotechnology , protein domain , biology , chemistry , gene , biochemistry , enzyme
Vasohibins (VASH1 and VASH2) are recently identified regulators of angiogenesis and cancer cell functions. They are secreted proteins without any classical secretion signal sequences, and are thought to be secreted instead via an unconventional protein secretion (UPS) pathway in a small vasohibin‐binding protein (SVBP)‐dependent manner. However, the precise mechanism of SVBP‐dependent UPS is poorly understood. In this study, we identified a novel UPS regulatory system in which essential domain architecture (VASH‐PS) of VASHs, comprising regions VASH1 91–180 and VASH2 80–169 , regulate the cytosolic punctate structure formation in the absence of SVBP. We also demonstrate that SVBP form a complex with VASH1 through the VASH1 274–282 (SIa), VASH1 139‐144 (SIb), and VASH1 133–137 (SIc), leading to the dispersion in the cytosol and extracellular release of VASH1. The amino acid sequences of VASH‐SIa and VASH‐PS, containing SIb and SIc, are highly conserved among VASH family members in vertebrates, suggesting that SVBP‐dependent UPS may be common within the VASH family. This novel UPS regulatory system may open up new avenues for understanding fundamental protein secretion in vertebrates.