title: Domain architecture of vasohibins required for their chaperone-dependent unconventional extracellular release.
abstract: 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 VASH191-180and VASH280-169, regulate the cytosolic punctate structure formation in the absence of SVBP. We also demonstrate that SVBP form a complex with VASH1 through the VASH1274-282(SIa), VASH1139-144(SIb), and VASH1133-137(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.
authors.affiliation: Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kadonosono
authors.affiliation: Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
authors.forename: Wanaporn
authors.initials: W
authors.lastname: Yimchuen
authors.affiliation: Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsubaki
authors.affiliation: Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Shiozawa
authors.affiliation: Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, 980-8575, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuchimaru
authors.affiliation: Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, 980-8575, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
authors.forename: Shinae
authors.initials: S
authors.lastname: Kizaka-Kondoh
mesh_terms: D042501:Angiogenic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains
chemical_list: D042501:Angiogenic Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; C554361:SVBP protein, human; C493181:VASH1 protein, human; C574858:VASH2 protein, human
keywords: molecular chaperon; punctate structure formation; unconventional protein secretion; vasohibins