title: N-Terminal signal sequence is required for cellular trafficking and hyaluronan-depolymerization of KIAA1199.
abstract: Recently, we disclosed that KIAA1199-mediated hyaluronan (HA) depolymerization requires an acidic cellular microenvironment (e.g. clathrin-coated vesicles or early endosomes), but no information about the structural basis underlying the cellular targeting and functional modification of KIAA1199 was available. Here, we show that the cleavage of N-terminal 30 amino acids occurs in functionally matured KIAA1199, and the deletion of the N-terminal portion results in altered intracellular trafficking of the molecule and loss of cellular HA depolymerization. These results suggest that the N-terminal portion of KIAA1199 functions as a cleavable signal sequence required for proper KIAA1199 translocation and KIAA1199-mediated HA depolymerization.
authors.affiliation: Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., 3-28, 5-chome, Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan. Electronic address: yoshida.hiroyuki@kanebocos.co.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., 3-28, 5-chome, Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Nagaoka
authors.affiliation: Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., 3-28, 5-chome, Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., 3-28, 5-chome, Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Tobiishi
authors.affiliation: Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., 3-28, 5-chome, Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sugiyama
authors.affiliation: Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., 3-28, 5-chome, Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D058105:Polymerization; D021382:Protein Sorting Signals; D021381:Protein Transport / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D017384:Sequence Deletion
chemical_list: D021382:Protein Sorting Signals; D011506:Proteins; D006820:Hyaluronic Acid; C491433:CEMIP protein, human; D006821:Hyaluronoglucosaminidase; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
keywords: CPC; Catabolism; DMEM; DTT; Dulbecco’s Modified Eagle’s Medium; ER; Endo H; FA; FBS; GAPDH; HA; HEK; HYAL; Hyaluronan; KIAA1199; LDS; N-Glycosylation; ORF; PBS; PBS containing 0.05% (vol/vol) Tween 20; PBS-T; PDI; Post-translational modification; SDS; Signal sequence; cetylpyridinium chloride; dithiothreitol; endo-β-N-acetylglucosaminidase H; endoplasmic reticulum; fetal bovine serum; fluoresceinamine; glyceraldehyde 3-phosphate dehydrogenase; human embryonic kidney; hyaluronan; hyaluronidase; lithium dodecyl sulfate; open reading frame; phosphate-buffered saline; protein disulfide isomerase; sodium dodecyl sulfate