title: Identification of a novel ADAMTS9/GON-1 function for protein transport from the ER to the Golgi.
abstract: A disintegrin-like and metalloprotease with thrombospondin type I motif (ADAMTS9) is a member of the secreted metalloprotease family that is believed to digest extracellular matrix (ECM) proteins outside of cells. Its Caenorhabditis elegans orthologue, GON-1, is involved in ECM degradation and is required for gonad morphogenesis. ADAMTS9 and GON-1 have similar domain structures, and both have a unique C-terminal domain called the "GON domain," whose function remains unknown. Here we show that down-regulation of human ADAMTS9 and C. elegans GON-1 results in the inhibition of protein transport from the endoplasmic reticulum (ER) to the Golgi. This phenotype was rescued by the expression of the GON domain localizing in the ER in human cells and C. elegans. We propose a novel function of ADAMTS9 and GON-1 in the ER that promotes protein transport from the ER to the Golgi. This function is GON-domain dependent but protease activity independent.
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo 162-8666, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Yoshina
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Sakaki
authors.forename: Aki
authors.initials: A
authors.lastname: Yonezumi-Hayashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Gengyo-Ando
authors.forename: Hideshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Iino
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071119:ADAMTS9 Protein; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D029742:Caenorhabditis elegans Proteins; D051722:ADAM Proteins; D000071119:ADAMTS9 Protein; C412869:ADAMTS9 protein, human; C119674:GON-1 protein, C elegans; D008666:Metalloendopeptidases