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Electrostatic plasma membrane targeting contributes to Dlg function in cell polarity and tumorigenesis
1Department of Cell Biology, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA.
Development (Cambridge, England)
|March 10, 2021
Summary
Discs large (Dlg) protein localization to the plasma membrane is crucial for cell polarity and tumor suppression. This study reveals Dlg uses electrostatic interactions with the plasma membrane, regulated by phosphorylation and Scrib, to achieve this critical localization.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Discs large (Dlg) is a conserved tumor suppressor and polarity protein essential for epithelial cell function.
- Dlg's plasma membrane (PM)/cortical localization is critical for its roles in polarity and tumorigenesis, but the targeting mechanisms are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms by which Dlg is targeted to the plasma membrane.
- To investigate the role of electrostatic interactions in Dlg's PM localization and function.
Main Methods:
- Analysis of Dlg's polybasic domain and its interaction with phosphoinositides (PI4P and PI(4,5)P2).
- Assessment of Dlg's PM localization in epithelial cells using various experimental approaches.
- Investigation of Dlg's regulation by phosphorylation and its interaction with Scrib.
Main Results:
- Dlg possesses a positively charged polybasic domain that electrostatically binds to PM phosphoinositides PI4P and PI(4,5)P2.
- This electrostatic targeting significantly contributes to Dlg's PM localization and is essential for its function in polarity and tumor suppression.
- Dlg's PM targeting is modulated by potential phosphorylation-dependent allosteric regulation and enhanced by interactions with Scrib.
Conclusions:
- Electrostatic targeting of the plasma membrane by Dlg's polybasic domain is a key mechanism for its localization and function.
- Phosphorylation and interaction with Scrib regulate Dlg's electrostatic PM targeting.
- These findings underscore the importance of electrostatic interactions in the regulation of cell polarity proteins.
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