title: Membrane phosphatidylserine regulates surface charge and protein localization.
abstract: 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.
authors.affiliation: Division of Cell Biology, Hospital for Sick Children, Toronto M5G 1X8, Canada.
authors.forename: Tony
authors.initials: T
authors.lastname: Yeung
authors.forename: Gary E
authors.initials: GE
authors.lastname: Gilbert
authors.forename: Jialan
authors.initials: J
authors.lastname: Shi
authors.forename: John
authors.initials: J
authors.lastname: Silvius
authors.forename: Andras
authors.initials: A
authors.lastname: Kapus
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005453:Fluorescence; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007425:Intracellular Membranes / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D018613:Microscopy, Confocal; D008894:Milk Proteins / Q000378:metabolism; D015388:Organelles / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D008894:Milk Proteins; D010718:Phosphatidylserines; D011993:Recombinant Fusion Proteins