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Transport Pathways That Contribute to the Cellular Distribution of Phosphatidylserine

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisReviewForskningpeer review


  • Guillaume Lenoir, Universite Paris-Saclay
  • ,
  • Juan Martín D’Ambrosio, Universite de Montpellier
  • ,
  • Thibaud Dieudonné
  • ,
  • Alenka Čopič, Universite de Montpellier

Phosphatidylserine (PS) is a negatively charged phospholipid that displays a highly uneven distribution within cellular membranes, essential for establishment of cell polarity and other processes. In this review, we discuss how combined action of PS biosynthesis enzymes in the endoplasmic reticulum (ER), lipid transfer proteins (LTPs) acting within membrane contact sites (MCS) between the ER and other compartments, and lipid flippases and scramblases that mediate PS flip-flop between membrane leaflets controls the cellular distribution of PS. Enrichment of PS in specific compartments, in particular in the cytosolic leaflet of the plasma membrane (PM), requires input of energy, which can be supplied in the form of ATP or by phosphoinositides. Conversely, coupling between PS synthesis or degradation, PS flip-flop and PS transfer may enable PS transfer by passive flow. Such scenario is best documented by recent work on the formation of autophagosomes. The existence of lateral PS nanodomains, which is well-documented in the case of the PM and postulated for other compartments, can change the steepness or direction of PS gradients between compartments. Improvements in cellular imaging of lipids and membranes, lipidomic analysis of complex cellular samples, reconstitution of cellular lipid transport reactions and high-resolution structural data have greatly increased our understanding of cellular PS homeostasis. Our review also highlights how budding yeast has been instrumental for our understanding of the organization and transport of PS in cells.

TidsskriftFrontiers in Cell and Developmental Biology
StatusUdgivet - sep. 2021

Bibliografisk note

Funding Information:
We thank Bruno Antonny, Guillaume Drin, Takeshi Harayama, and Nicolas-Fr?d?ric Lipp for helpful discussions and comments on the manuscript. Funding. This work was supported by the Agence Nationale de la Recherche Grant (ANR-20-CE13-0030-02), the CNRS and Universit? Paris-Saclay. TD received financial support from Marie Curie Individual Fellowship (LivFlip, grant agreement 101024542, H2020-MSCA-IF-2020).

Publisher Copyright:
© Copyright © 2021 Lenoir, D’Ambrosio, Dieudonné and Čopič.

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