Interrelationship between non-vesicular transport of sterols and their distribution between rafts and the non-raft phase of the plasma membrane

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Abstract

Sterols significantly affect the barrier properties of the membrane. This probably explains the fact that their concentration is maximal in the PM (plasma membrane). In combination with sphingolipids, sterols form rafts - bilayer regions whose physicochemical properties differ from those in the surrounding membrane. Thus, in the presence of rafts in the membrane, membrane proteins can choose the lipid environment optimal for their functioning, best suited in terms of thickness and rigidity of the bilayer, spontaneous curvature and lateral pressure profile. Sterols and sphingolipids in rafts are in ratios close to stoichiometric. Theoretically, excess sterol outside rafts can critically reduce the degree of ordering of phospholipid ordering. Sterols are synthesized in the endoplasmic reticulum (ER). An active, against the concentration gradient, transport of sterols from the ER to the PM is carried out by proteins of the Osh family. Lam proteins carry out passive reverse transport of sterols from the PM to the ER. Inactivation of Osh proteins does not reduce the total level of sterols in the PM, but, in an unclear way, reduces the rate of their movement inside the PM. Therefore, the vesicular transport of sterols from the ER to the PM is probably more active than the non-vesicular one carried out by Osh proteins. Since sterols are more firmly anchored in rafts than outside them, and are also sterically less accessible, we suggest that Lam proteins transport excess sterols from the non-raft phase of the PM to the ER, and Osh proteins return them to the PM. In this way, the rotation of sterols between the non-raft part of the PM and rafts can be driven, with the enrichment of the latter. It is possible that with a decrease in the concentration of sterol in the non-raft part of the membrane, the speed of the Lam proteins decreases since the degree of ordering of phospholipids and, consequently, the strength of retention of the sterol molecule in the membrane increases. It is possible that homeostasis of the concentration and distribution of sterol in the PM is maintained in this way.

About the authors

S. S. Sokolov

Lomonosov Moscow State University

Author for correspondence.
Email: sviatoslav.sokolov@gmail.com

Belozersky Institute of Physico-Chemical Biology

Russian Federation, 119991 Moscow

A. N. Zyrina

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences

Email: sviatoslav.sokolov@gmail.com
Russian Federation, 108819 Moscow

S. A. Akimov

Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences

Email: sviatoslav.sokolov@gmail.com
Russian Federation, 119071 Moscow

F. F. Severin

Lomonosov Moscow State University

Email: sviatoslav.sokolov@gmail.com

Belozersky Institute of Physico-Chemical Biology

Russian Federation, 119991 Moscow

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