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Membrane Phosphatidylserine Regulates Surface Charge and Protein Localization
Tony Yeung,1Gary E. Gilbert,2Jialan Shi,2John Silvius,3Andras Kapus,4Sergio Grinstein1*
Electrostatic interactions with negatively charged membranescontribute to the subcellular targeting of proteins with polybasicclusters or cationic domains. Although the anionic phospholipidphosphatidylserine is comparatively abundant, its contributionto the surface charge of individual cellular membranes is unknown,partly because of the lack of reagents to analyze its distributionin intact cells. We developed a biosensor to study the subcellulardistribution of phosphatidylserine and found that it binds thecytosolic leaflets of the plasma membrane, as well as endosomesand lysosomes. The negative charge associated with the presenceof phosphatidylserine directed proteins with moderately positivecharge to the endocytic pathway. More strongly cationic proteins,normally associated with the plasma membrane, relocalized toendocytic compartments when the plasma membrane surface chargedecreased on calcium influx.
1 Division of Cell Biology, The Hospital for Sick Children, Toronto M5G 1X8, Canada. 2 Department of Medicine, Department of Veterans Affairs, VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. 3 Department of Biochemistry, McGill University, Montreal H3G 1Y6, Canada. 4 Keenan Research Center in the Li Ka Sheng Knowledge Institute of St. Michael's Hospital and Department of Surgery, University of Toronto, Toronto M5B 1W8, Canada.
* To whom correspondence should be addressed. E-mail: sga{at}sickkids.ca
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