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Concept
Membrane contact site
Summary
Membrane contact sites (MCS) are close appositions between two organelles. Ultrastructural studies typically reveal an intermembrane distance in the order of the size of a single protein, as small as 10 nm or wider, with no clear upper limit. These zones of apposition are highly conserved in evolution. These sites are thought to be important to facilitate signalling, and they promote the passage of small molecules, including ions, lipids and (discovered later) reactive oxygen species. MCS are important in the function of the endoplasmic reticulum (ER), since this is the major site of lipid synthesis within cells. The ER makes close contact with many organelles, including mitochondria, Golgi, endosomes, lysosomes, peroxisomes, chloroplasts and the plasma membrane. Both mitochondria and sorting endosomes undergo major rearrangements leading to fission where they contact the ER. Sites of close apposition can also form between most of these organelles most pairwise combinations. First mentions of these contact sites can be found in papers published in the late 1950s mainly visualized using electron microscopy (EM) techniques. Copeland and Dalton described them as “highly specialized tubular form of endoplasmic reticulum in association with the mitochondria and apparently in turn, with the vascular border of the cell”.
MCSs between ER and PM exist in different cell types from neurons to muscle cells, from Homo sapiens to Saccharomyces cerevisiae. Some studies showed that more than 1000 contact sites are present in every yeast cell and the distance between the lipid bilayer ranges from 10 to 25 nm (the order of the size of a single protein). PM-ER contact sites have been linked to the main functions of MCS: lipid synthesis, lipid trafficking, and calcium homeostasis. A set of molecular tools (e.g., LiMETER and MAPPER) have been developed to label and manipulate the formation of ER-PM junctions in living cells.
The uneven distribution of sterols among the membranes of the cell organelles, depends largely on non-vesicular route of transfer.
Official source
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