論文 - 詳細
RRC ID | 60781 |
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著者 | Osada Y, Suzuki T, Mizuta H, Mori K, Miura K, Dohmae N, Simizu S. |
タイトル | The fibrinogen C-terminal domain is seldom C-mannosylated but its C-mannosylation is important for the secretion of microfibril-associated glycoprotein 4. |
ジャーナル | Biochim Biophys Acta Gen Subj |
Abstract |
BACKGROUND:C-mannosylation is the one of glycosylations. Microfibril-associated glycoprotein 4 (MFAP4), an important protein for tissue homeostasis and cell adhesion, contains a consensus sequence of C-mannosylation in its fibrinogen C-terminal domain. In this study, we sought to demonstrate that fibrinogen C-terminal domain is a new substrate domain for C-mannosylation. METHODS:We established an MFAP4-overexpresssing HT1080 cell line and purified recombinant MFAP4 protein from the conditioned medium for LC-MS/MS analysis. Subcellular localization of MFAP4 was observed under confocal fluorescence microscope. RESULTS:We found that MFAP4 is C-mannosylated at Trp235 in the fibrinogen C-terminal domain by LC-MS/MS. To determine the functions of the C-mannosylation of MFAP4, we established a C-mannosylation-defective mutant MFAP4-overexpresssing HT1080 cell line and measured its secretion of MFAP4. The secretion of MFAP4 decreased significantly in the C-mannosylation-defective mutant MFAP4-overexpresssing cell line versus wild-type cells. Moreover, co-transfection experiments indicated that C-mannosylated MFAP4 accelerated its secretion. CONCLUSIONS:Our results demonstrate that the fibrinogen C-terminal domain is a novel C-mannosylation domain and that the C-mannosylation of MFAP4 is important for its secretion. GENERAL SIGNIFICANCE:These results suggest that C-mannosylation has a role for dominant effect for MFAP4 secretion. |
巻・号 | 1864(9) |
ページ | 129637 |
公開日 | 2020-9-1 |
DOI | 10.1016/j.bbagen.2020.129637 |
PII | S0304-4165(20)30149-5 |
PMID | 32442478 |
MeSH | Carrier Proteins / metabolism* Cell Line, Tumor Extracellular Matrix Proteins / metabolism* Fibrinogen / chemistry* Fibrinogen / metabolism* Glycoproteins / metabolism* Humans Mannose / metabolism* Protein Domains Protein Transport |
IF | 3.422 |
引用数 | 0 |
リソース情報 | |
遺伝子材料 | Genome Net Work Project Human cDNA clone IRAK141E15 (HGX056511) pCI-neo MFAP4-MH wt (RDB18691) pCI-neo MFAP4-HA WF (RDB18692) |