| Autor: |
Qiang Yue, Otor Al-Khalili, Auriel Moseley, Masaaki Yoshigi, Brandi Michele Wynne, Heping Ma, Douglas C. Eaton |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Biology, Vol 11, Iss 12, p 1694 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2079-7737 |
| DOI: |
10.3390/biology11121694 |
| Popis: |
We examined the interaction of a membrane-associated protein, MARCKS-like Protein-1 (MLP-1), and an ion channel, Epithelial Sodium Channel (ENaC), with the anionic lipid, phosphatidylinositol 4, 5-bisphosphate (PIP2). We found that PIP2 strongly activates ENaC in excised, inside-out patches with a half-activating concentration of 21 ± 1.17 µM. We have identified 2 PIP2 binding sites in the N-terminus of ENaC β and γ with a high concentration of basic residues. Normal channel activity requires MLP-1’s strongly positively charged effector domain to electrostatically sequester most of the membrane PIP2 and increase the local concentration of PIP2. Our previous data showed that ENaC covalently binds MLP-1 so PIP2 bound to MLP-1 would be near PIP2 binding sites on the cytosolic N terminal regions of ENaC. We have modified the charge structure of the PIP2 –binding domains of MLP-1 and ENaC and showed that the changes affect membrane localization and ENaC activity in a way consistent with electrostatic theory. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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