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Physiological Reviews, Vol. 81, No. 4, October 2001, pp. 1689-1723
Copyright ©2001 by the American Physiological Society
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam; and Department of Cell Biology, Utrecht University School of Medicine, Utrecht, The Netherlands
Holthuis, Joost C. M.,
Thomas Pomorski,
René J. Raggers,
Hein Sprong, and
Gerrit Van Meer.
The Organizing Potential of Sphingolipids in Intracellular
Membrane Transport. Physiol. Rev. 81: 1689-1723, 2001.
Eukaryotes are characterized by
endomembranes that are connected by vesicular transport along secretory
and endocytic pathways. The compositional differences between the
various cellular membranes are maintained by sorting events, and it has
long been believed that sorting is based solely on protein-protein
interactions. However, the central sorting station along the secretory
pathway is the Golgi apparatus, and this is the site of synthesis of
the sphingolipids. Sphingolipids are essential for eukaryotic life, and
this review ascribes the sorting power of the Golgi to its capability
to act as a distillation apparatus for sphingolipids and cholesterol.
As Golgi cisternae mature, ongoing sphingolipid synthesis attracts
endoplasmic reticulum-derived cholesterol and drives a
fluid-fluid lipid phase separation that segregates sphingolipids and sterols from unsaturated glycerolipids into lateral domains. While
sphingolipid domains move forward, unsaturated glycerolipids are
retrieved by recycling vesicles budding from the sphingolipid-poor environment. We hypothesize that by this mechanism, the composition of
the sphingolipid domains, and the surrounding membrane changes along
the cis-trans axis. At the same time the membrane
thickens. These features are recognized by a number of membrane
proteins that as a consequence of partitioning between domain and
environment follow the domains but can enter recycling vesicles at any
stage of the pathway. The interplay between protein- and
lipid-mediated sorting is discussed.
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