title: Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes.
abstract: Phosphatidylserine (PS) is a relatively minor constituent of biological membranes. Despite its low abundance, PS in the plasma membrane (PM) plays key roles in various phenomena such as the coagulation cascade, clearance of apoptotic cells, and recruitment of signaling molecules. PS also localizes in endocytic organelles, but how this relates to its cellular functions remains unknown. Here we report that PS is essential for retrograde membrane traffic at recycling endosomes (REs). PS was most concentrated in REs among intracellular organelles, and evectin-2 (evt-2), a protein of previously unknown function, was targeted to REs by the binding of its pleckstrin homology (PH) domain to PS. X-ray analysis supported the specificity of the binding of PS to the PH domain. Depletion of evt-2 or masking of intracellular PS suppressed membrane traffic from REs to the Golgi. These findings uncover the molecular basis that controls the RE-to-Golgi transport and identify a unique PH domain that specifically recognizes PS but not polyphosphoinositides.
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Uchida
authors.forename: Junya
authors.initials: J
authors.lastname: Hasegawa
authors.forename: Daniel
authors.initials: D
authors.lastname: Chinnapen
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Seiji
authors.initials: S
authors.lastname: Okazaki
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kato
authors.forename: Soichi
authors.initials: S
authors.lastname: Wakatsuki
authors.forename: Ryo
authors.initials: R
authors.lastname: Misaki
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Kuwahara
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Kojiro
authors.initials: K
authors.lastname: Mukai
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: David
authors.initials: D
authors.lastname: Sheff
authors.forename: Wayne I
authors.initials: WI
authors.lastname: Lencer
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008954:Models, Biological; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034622:RNA Interference; D014709:Vero Cells
chemical_list: D008565:Membrane Proteins; C118742:PLEKHB2 protein, human; D010718:Phosphatidylserines; D049452:Green Fluorescent Proteins