Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes

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

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15846-15851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number38
DOIs
Publication statusPublished - 2011 Oct 20
Externally publishedYes

Keywords

  • Cholera toxin
  • Endocytosis

ASJC Scopus subject areas

  • General

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