N-Terminal signal sequence is required for cellular trafficking and hyaluronan-depolymerization of KIAA1199
- FEBS Lett. 2014 Jan 3;588(1):111-6. doi: 10.1016/j.febslet.2013.11.017.
Affiliations
- 1. Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., 3-28, 5-chome, Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan. Electronic address: [email protected].
- 2. Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., 3-28, 5-chome, Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan.
PMID: 24269685
DOI: 10.1016/j.febslet.2013.11.017
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.
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.