Calcium-dependent and -independent lipid transfer mediated by tricalbins in yeast
| Autor: | Chenlu Li, Tiantian Qian, Chun Wan, Ruyue He, Haijia Yu, Yinghui Liu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
E-Syt extended-synaptotagmin MCS membrane contact site membrane contact sites Saccharomyces cerevisiae FRET Förster resonance energy transfer plasma membrane NBD 7-nitro-2 1 3-benzoxadiazole PE phosphatidylethanolamine Biochemistry LTP lipid transfer protein ER endoplasmic reticulum PC phosphatidylcholine 03 medical and health sciences chemistry.chemical_compound tricalbin PI phosphoinositide lipid transfer Molecular Biology Phospholipids Lipid Transport Phosphatidylethanolamine 030102 biochemistry & molecular biology Cortical endoplasmic reticulum SMP synaptotagmin-like mitochondrial lipid-binding protein Endoplasmic reticulum Calcium-Binding Proteins Cell Membrane Biological Transport SMP Cell Biology Phosphatidylserine PS phosphatidylserine cER cortical endoplasmic reticulum Membrane contact site endoplasmic reticulum 030104 developmental biology Förster resonance energy transfer chemistry PM plasma membrane Biophysics Calcium lipids (amino acids peptides and proteins) Plant lipid transfer proteins Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.100729 |
| Popis: | Membrane contact sites (MCSs) formed between the endoplasmic reticulum (ER) and the plasma membrane (PM) provide a platform for nonvesicular lipid exchange. The ER-anchored tricalbins (Tcb1, Tcb2, and Tcb3) are critical tethering factors at ER–PM MCSs in yeast. Tricalbins possess a synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain and multiple Ca2+-binding C2 domains. Although tricalbins have been suggested to be involved in lipid exchange at the ER–PM MCSs, it remains unclear whether they directly mediate lipid transport. Here, using in vitro lipid transfer assays, we discovered that tricalbins are capable of transferring phospholipids between membranes. Unexpectedly, while its lipid transfer activity was markedly elevated by Ca2+, Tcb3 constitutively transferred lipids even in the absence of Ca2+. The stimulatory activity of Ca2+ on Tcb3 required intact Ca2+-binding sites on both the C2C and C2D domains of Tcb3, while Ca2+-independent lipid transport was mediated by the SMP domain that transferred lipids via direct interactions with phosphatidylserine and other negatively charged lipid molecules. These findings establish tricalbins as lipid transfer proteins, and reveal Ca2+-dependent and -independent lipid transfer activities mediated by these tricalbins, providing new insights into their mechanism in maintaining PM integrity at ER–PM MCSs. |
| Databáze: | OpenAIRE |
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