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- W2968277001 endingPage "129414" @default.
- W2968277001 startingPage "129414" @default.
- W2968277001 abstract "Unlike other cadherins, T-cadherin does not mediate strong cell-cell adhesion. It has two soluble ligands: low density lipoprotein (LDL) and high-molecular-weight (HMW) adiponectin. LDL binding to T-cadherin induces calcium signaling, migration, and proliferation, and has proatherogenic effects, but adiponectin binding promotes antiatherogenic effects. The reasons for this difference and mechanism of signal transduction by glycosylphosphatidylinositol (GPI)-anchored T-cadherin are unknown. We compared the ability of LDL and HMW adiponectin to induce calcium signaling, T-cadherin clustering and internalization. We measured calcium signaling in smooth muscle cells and T-cadherin expressing HEK293 using single-cell imaging. To study receptor clustering, we tested three different T-cadherin labeling strategies and then utilized confocal microscopy and flow cytometry assays based on Förster resonance energy transfer (FRET). Enzymatically labeled T-cadherin retained its cellular localization and physiological activity, features that were otherwise affected by fluorescent proteins and antibodies. This labeling method allowed us to study T-cadherin clustering dynamics at the cell surface. HMW adiponectin induced the formation of stable T-cadherin clusters while LDL induced short-lived clusters. Cellular responses were also different: LDL triggered cholesterol- and actin-dependent calcium signaling without internalization while adiponectin promoted the opposite effect. We revealed distinct ligand-specific T-cadherin clustering and its ability to induce internalization or intracellular calcium signaling that likely explains the different physiological effects of LDL and HMW adiponectin. This work highlights the importance of GPI-anchored receptor clustering dynamics in mediating cellular responses. Different ligands can induce different effects in an identical cell via the same receptor." @default.
- W2968277001 created "2019-08-22" @default.
- W2968277001 creator A5021300992 @default.
- W2968277001 creator A5035482823 @default.
- W2968277001 creator A5057461148 @default.
- W2968277001 creator A5073762498 @default.
- W2968277001 creator A5079214942 @default.
- W2968277001 date "2019-11-01" @default.
- W2968277001 modified "2023-10-01" @default.
- W2968277001 title "Different spatiotemporal organization of GPI-anchored T-cadherin in response to low-density lipoprotein and adiponectin" @default.
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- W2968277001 doi "https://doi.org/10.1016/j.bbagen.2019.129414" @default.
- W2968277001 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31404618" @default.
- W2968277001 hasPublicationYear "2019" @default.
- W2968277001 type Work @default.