Journal Article

Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes

Sheff, David, Okazaki, Seiji, Wakatsuki, Soichi, Uchida, Yasunori, Inoue, Takao, Taguchi, Tomohiko, Koike, Masato, Mukai, Kojiro, Nishikawa, Kiyotaka, Hasegawa, Junya, Kato, Ryuichi, Nakagawa, Takatoshi, Miyoshi, Eiji, Kuwahara, Ryusuke, Misaki, Ryo, Chinnapen, Daniel, Arai, Hiroyuki, Iemura, Shun-ichiro, Lencer, Wayne I, Natsume, Tohru, Taniguchi, Naoyuki, Uchiyama, Yasuo

2011

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: abundance / Animals / Apoptosis / Biological membranes / Biological Sciences / Cell membranes / Chlorocebus aethiops / Cholera / coagulation / COS Cells / Crystallography, X-Ray / Endosomes / Endosomes - metabolism / Endosomes - ultrastructure / Golgi Apparatus - metabolism / Green Fluorescent Proteins - genetics / Green Fluorescent Proteins - metabolism / HeLa Cells / Humans / Intracellular Membranes - metabolism / Intracellular Membranes - ultrastructure / Kidney cells / Ligands / Membrane Proteins - chemistry / Membrane Proteins - genetics / Membrane Proteins - metabolism / Membranes / Microscopy, Fluorescence / Microscopy, Immunoelectron / Models, Biological / Molecules / Phosphatidylserines - chemistry / Phosphatidylserines - metabolism / Plasma / plasma membrane / pleckstrin / Protein Binding / Protein Structure, Tertiary / Protein Transport / Proteins / recruitment / Recycling / RNA Interference / Small interfering RNA / Toxins / Traffic / Vero Cells / Waste management / X-radiation