Phospholipid exchange shows insulin receptor activity is supported by both the propensity to form wide bilayers and ordered raft domains
| Autor: | W. Todd Miller, Pavana Suresh, Erwin London |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipid Bilayers
bilayer width Biochemistry Micelle liquid ordered chemistry.chemical_compound DDM n-dodecyl-β-D maltopyranoside PC phosphatidylcholine MβCD methyl-β-cyclodextrin POPC 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine eSM egg SM insulin receptor Lipid raft Phospholipids MαCD methyl-α-cyclodextrin lipid exchange lipid rafts Ld liquid disordered biology SOV sodium orthovanadate Bilayer CMC critical micelle concentration DPPC 1 2-dipalmitoyl-sn-glycero-3-phosphocholine Raft membrane lipid IR insulin receptor DM n-decyl-β-D maltopyranoside lipids (amino acids peptides and proteins) DLPC 1 2-dilauroyl-sn-glycero-3-phosphocholine autophosphorylation Sphingomyelin Research Article insulin Phospholipid CHO Cells DMEM Dulbecco’s modified eagle medium Cricetulus Membrane Microdomains PBS phosphate buffered saline membrane structure Lo liquid ordered Animals DMPC 1 2-dimyristoyl-sn-glycero-3-phosphocholine HDM n-hexadecyl-β-D-maltopyranoside Molecular Biology POPC SM sphingomyelin DSPC 1 2-distearoyl-sn-glycero-3-phosphocholine Cell Biology TDM n-tetradecyl-β-D maltopyranoside Receptor Insulin DOPC 1 2-dioleoyl-sn-glycero-3-phosphocholine Insulin receptor chemistry cyclodextrin Biophysics biology.protein bSM brain SM |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | Insulin receptor (IR) is a membrane tyrosine kinase that mediates the response of cells to insulin. IR activity has been shown to be modulated by changes in plasma membrane lipid composition, but the properties and structural determinants of lipids mediating IR activity are poorly understood. Here, using efficient methyl-alpha-cyclodextrin mediated lipid exchange, we studied the effect of altering plasma membrane outer leaflet phospholipid composition upon the activity of IR in mammalian cells. After substitution of endogenous lipids with lipids having an ability to form liquid ordered (Lo) domains (sphingomyelins) or liquid disordered (Ld) domains (unsaturated phosphatidylcholines (PCs)), we found that the propensity of lipids to form ordered domains is required for high IR activity. Additional substitution experiments using a series of saturated PCs showed that IR activity increased substantially with increasing acyl chain length, which increases both bilayer width and the propensity to form ordered domains. Incorporating purified IR into alkyl maltoside micelles with increasing hydrocarbon lengths also increased IR activity, but more modestly than by increasing lipid acyl chain length in cells. These results suggest that the ability to form Lo domains as well as wide bilayer width contributes to increased IR activity. Inhibition of phosphatases showed that some of the lipid dependence of IR activity upon lipid structure reflected protection from phosphatases by lipids that support Lo domain formation. These results are consistent with a model in which a combination of bilayer width and ordered domain formation modulates IR activity via IR conformation and accessibility to phosphatases. |
| Databáze: | OpenAIRE |
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