Tony Yeung1,2,3,4, Gary E. Gilbert1,2,3,4, Jialan Shi1,2,3,4, John R. Silvius1,2,3,4, András Kapùs1,2,3,4, Sergio Grinstein1,2,3,4
1Department of Biochemistry, McGill University, Montreal H3G 1Y6, Canada
2Department of Medicine, Department of Veterans Affairs, VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
3Division of Cell Biology, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
4Keenan 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.
Tóm tắt
Electrostatic interactions with negatively charged membranes contribute to the subcellular targeting of proteins with polybasic clusters or cationic domains. Although the anionic phospholipid phosphatidylserine is comparatively abundant, its contribution to the surface charge of individual cellular membranes is unknown, partly because of the lack of reagents to analyze its distribution in intact cells. We developed a biosensor to study the subcellular distribution of phosphatidylserine and found that it binds the cytosolic leaflets of the plasma membrane, as well as endosomes and lysosomes. The negative charge associated with the presence of phosphatidylserine directed proteins with moderately positive charge to the endocytic pathway. More strongly cationic proteins, normally associated with the plasma membrane, relocalized to endocytic compartments when the plasma membrane surface charge decreased on calcium influx.
