Reference - Detail
| RRC ID | 65882 |
|---|---|
| Author | Fukuda S, Kita S, Obata Y, Fujishima Y, Nagao H, Masuda S, Tanaka Y, Nishizawa H, Funahashi T, Takagi J, Maeda N, Shimomura I. |
| Title | The unique prodomain of T-cadherin plays a key role in adiponectin binding with the essential extracellular cadherin repeats 1 and 2. |
| Journal | J Biol Chem |
| Abstract |
Adiponectin, an adipocyte-derived circulating protein, accumulates in the heart, vascular endothelium, and skeletal muscles through an interaction with T-cadherin (T-cad), a unique glycosylphosphatidylinositol-anchored cadherin. Recent studies have suggested that this interaction is essential for adiponectin-mediated cardiovascular protection. However, the precise protein-protein interaction between adiponectin and T-cad remains poorly characterized. Using ELISA-based and surface plasmon analyses, we report here that T-cad fused with IgG Fc as a fusion tag by replacing its glycosylphosphatidylinositol-anchor specifically bound both hexameric and larger multimeric adiponectin with a dissociation constant of ∼1.0 nm and without any contribution from other cellular or serum factors. The extracellular T-cad repeats 1 and 2 were critical for the observed adiponectin binding, which is required for classical cadherin-mediated cell-to-cell adhesion. Moreover, the 130-kDa prodomain-bearing T-cad, uniquely expressed on the cell surface among members of the cadherin family and predominantly increased by adiponectin, contributed significantly to adiponectin binding. Inhibition of prodomain-processing by a prohormone convertase inhibitor increased 130-kDa T-cad levels and also enhanced adiponectin binding to endothelial cells both by more preferential cell-surface localization and by higher adiponectin-binding affinity of 130-kDa T-cad relative to 100-kDa T-cad. The preferential cell-surface localization of 130-kDa T-cad relative to 100-kDa T-cad was also observed in normal mice aorta in vivo In conclusion, our study shows that a unique key feature of the T-cad prodomain is its involvement in binding of the T-cad repeats 1 and 2 to adiponectin and also demonstrates that adiponectin positively regulates T-cad abundance. |
| Volume | 292(19) |
| Pages | 7840-7849 |
| Published | 2017-5-12 |
| DOI | 10.1074/jbc.M117.780734 |
| PII | S0021-9258(20)41883-6 |
| PMID | 28325833 |
| PMC | PMC5427265 |
| MeSH | Adiponectin / chemistry* Adiponectin / genetics Animals CHO Cells Cadherins / chemistry* Calcium / chemistry Cell Adhesion Cell Membrane / metabolism Cricetinae Cricetulus Disulfides / chemistry Endothelial Cells / cytology Endothelial Cells / metabolism Enzyme-Linked Immunosorbent Assay Glycosylphosphatidylinositols / chemistry HEK293 Cells Humans Immunoglobulin G / chemistry Kinetics Male Mice Mice, Inbred C57BL Mice, Knockout Protein Binding Protein Domains Protein Interaction Mapping Surface Plasmon Resonance |
| IF | 4.238 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293(RCB1637) |