Regulation of N-glycosylation and secretion of Isthmin-1 by its C-mannosylation

Yoshimoto, Satoshi; Katayama, Kazuhiro; Suzuki, Takehiro; Dohmae, Naoshi; Simizu, Siro

doi:10.1016/j.bbagen.2020.129840

Cited by 14 publications

(9 citation statements)

References 35 publications

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“…There are four homologs of DPY19 (DPY19L1-L4) in mammals, and it has been demonstrated that DPY19L1 and DPY19L3 have a C -mannosyltransferase activity [ 11 , 12 ]. It has been revealed that C -mannosylation involves protein secretion, intracellular localization, and protein folding, which are similar with other forms of glycosylation [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]; however, the role of C -mannosyltransferases on biological events is still obscured.…”

Section: Introductionmentioning

confidence: 99%

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

et al. 2021

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DPY19L3 has been identified as a C-mannosyltransferase for thrombospondin type-1 repeat domain-containing proteins. In this study, we focused on the role of DPY19L3 in the myogenic differentiation of C2C12 mouse myoblast cells. We carried out DPY19L3 gene depletion using the CRISPR/Cas9 system. The result showed that these DPY19L3-knockout cells could not be induced for differentiation. Moreover, the phosphorylation levels of MEK/ERK and p70S6K were suppressed in the DPY19L3-knockout cells compared with that of parent cells, suggesting that the protein(s) that is(are) DPY19L3-mediated C-mannosylated and regulate(s) MEK/ERK or p70S6K signaling is(are) required for the differentiation.

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Section: Introductionmentioning

confidence: 99%

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

et al. 2021

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“…The TSR is related to cell migration, communication and tissue remodeling while the AMOP is involved in cell adhesion and angiogenesis ( 22 , 23 ). The TSR domain of ISM1 contains two consensus C-mannosylation sequences at Trp 223 and Trp 226 , which not only affects the secretion of ISM1 but also affects its N-glycosylation ( 24 ). The AMOP domain of ISM1 may mediate angiogenesis by regulating the interaction between ISM1 and αvβ5 integrin, function as proapoptotic ligands of cell-surface glucose-regulatory protein 78KDa (GRP78) ( 18 , 19 , 25 ).…”

Section: Location Gene and Protein Structurementioning

confidence: 99%

A brief overview about the adipokine: Isthmin-1

Zhang²,

Hu³

et al. 2022

Front. Cardiovasc. Med.

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“…The secretion levels of ADAMTS16 and UNC5A were reduced in C -mannosyltransferase-deficient cells, suggesting that secretion depends on C -mannosylation. In addition to UNC5A and ADAMTS16, C -mannosyltransferase-deficient cell lines and experimental substitution of Trp for non- C -mannosylated amino acids caused disturbance in the secretion of proteins, such as mucins (MUC5AC and MUC5B) [ 78 , 79 ], TSP-1 [ 50 ], mindin (Spondin2) [ 52 ], ADAMTSL1 [ 53 ], MIG-21 [ 54 ], ADAMTS13 [ 56 ], MIC2 [ 60 ], R-spondin1 [ 62 ], R-spondin3 [ 63 ], ADAMTS4 [ 67 ], Isthmin-1 [ 68 ], lipoprotein lipase [ 86 ], and microfibril-associated glycoprotein 4 (MFAP4) [ 87 ]. C -Mannosylation also regulated cell surface localization of IL-21R [ 71 ] and thrombopoietin receptor (TPOR) [ 72 ].…”

Section: Biochemical Aspects Of Protein C -Mannosylation and C -Man-trpmentioning

confidence: 99%

“…These results suggested that C -mannosylation could modulate various functions of enzymes in cells. In addition, C -mannosylation of Isthmin-1 affected its N -glycosylation [ 68 ]. N -Glycosylation of Isthmin-1 occurred in C -mannosylation-defective mutant cells, although wild-type Isthmin-1 was not N -glycosylated.…”

Section: Biochemical Aspects Of Protein C -Mannosylation and C -Man-trpmentioning

confidence: 99%

Protein C-Mannosylation and C-Mannosyl Tryptophan in Chemical Biology and Medicine

et al. 2021

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C-Mannosylation is a post-translational modification of proteins in the endoplasmic reticulum. Monomeric α-mannose is attached to specific Trp residues at the first Trp in the Trp-x-x-Trp/Cys (W-x-x-W/C) motif of substrate proteins, by the action of C-mannosyltransferases, DPY19-related gene products. The acceptor substrate proteins are included in the thrombospondin type I repeat (TSR) superfamily, cytokine receptor type I family, and others. Previous studies demonstrated that C-mannosylation plays critical roles in the folding, sorting, and/or secretion of substrate proteins. A C-mannosylation-defective gene mutation was identified in humans as the disease-associated variant affecting a C-mannosylation motif of W-x-x-W of ADAMTSL1, which suggests the involvement of defects in protein C-mannosylation in human diseases such as developmental glaucoma, myopia, and/or retinal defects. On the other hand, monomeric C-mannosyl Trp (C-Man-Trp), a deduced degradation product of C-mannosylated proteins, occurs in cells and extracellular fluids. Several studies showed that the level of C-Man-Trp is upregulated in blood of patients with renal dysfunction, suggesting that the metabolism of C-Man-Trp may be involved in human kidney diseases. Together, protein C-mannosylation is considered to play important roles in the biosynthesis and functions of substrate proteins, and the altered regulation of protein C-manosylation may be involved in the pathophysiology of human diseases. In this review, we consider the biochemical and biomedical knowledge of protein C-mannosylation and C-Man-Trp, and introduce recent studies concerning their significance in biology and medicine.

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Regulation of N-glycosylation and secretion of Isthmin-1 by its C-mannosylation

Cited by 14 publications

References 35 publications

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

A brief overview about the adipokine: Isthmin-1

Protein C-Mannosylation and C-Mannosyl Tryptophan in Chemical Biology and Medicine

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