Regulation of secretion and enzymatic activity of lipoprotein lipase by C-mannosylation.
Lipoprotein lipase (LPL) is a crucial enzyme in lipid metabolism and transport, and its enzymatic deficiency causes metabolic disorders, such as hypertriglyceridemia. LPL has one predicted C-mannosylation site at Trp417. In this study, we demonstrated that LPL is C-mannosylated at Trp417by mass spectrometry. Furthermore, by using wild-type and a C-mannosylation-defective mutant of LPL-overexpressing cell lines, we revealed that both secretion efficiency and enzymatic activity of C-mannosylation-defective mutant LPL were lower than those of wild-type. These data suggest the importance of C-mannosylation for LPL functions.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Sawako
S
Okamoto
Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura 285-8741, Japan.
Takeyoshi
T
Murano
Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako 351-0198, Japan.
Takehiro
T
Suzuki
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Shiho
S
Uematsu
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Yuki
Y
Niwa
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Yukiko
Y
Sasazawa
Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako 351-0198, Japan.
Naoshi
N
Dohmae
Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura 285-8741, Japan.
Hideaki
H
Bujo
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. Electronic address: simizu@applc.keio.ac.jp.
Siro
S
Simizu
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D015723:Gene Library; D006031:Glycosylation; D056945:Hep G2 Cells; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism*; D009154:Mutation; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D014364:Tryptophan; D008071:Lipoprotein Lipase; D008358:Mannose
C-mannosylation; Enzymatic activity; Glycosylation; Lipoprotein lipase; Secretion