Membrane contact sites (MCSs) are sites where the membranes of two different organelles come into close apposition (10–30 nm). Different classes of proteins populate MCSs including factors that act as tethers between the two membranes, proteins that use the MCSs for their function (mainly lipid or ion exchange), and regulatory proteins and enzymes that can act in trans across the MCSs. The ER-Golgi MCSs were visualized by electron microscopists early in the sixties but have remained elusive for decades due to a lack of suitable methodological approaches. Here we report recent progress in the study of this class of MCSs that has led to the identification of their main morphological features and of some of their components and roles. Among these, lipid transfer proteins and lipid exchange have been the most studied and understood so far. However, many unknowns remain regarding their regulation and their role in controlling key TGN functions such as sorting and trafficking as well as their relevance in physiological and pathological conditions.
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Cover Image
Cover Image
The cover image depicts a combination of a 3D reconstruction of ER-TGN contact sites by focus ion beam-scanning electron microscopy (FIB-SEM) and five images showing the visualization of the contacts by FRET/FLIM. The 3D reconstruction of the Golgi stack was generated from FIB-SEM tomography of a HepG2 cell using IMOD software. The ER cisterna is shown in red (with ribosomes as white circles), while the trans-most cisterna of the Golgi stack is shown in green (with emerging clathrin-coated buds decorated by pink dots). The five FLIM images are from HeLa cells expressing a TGN reporter (TGN46-GFP) and an ER reporter (mCherry-Cb5). The pseudocolour scale represents donor (i.e. GFP) lifetime (τ) values ranging from 1.8 (blue) to 2.7 ns (red) under conditions that destabilize (left) or stabilize ER-TGN contact sites. For further information, see the review by Venditti and colleagues (pp. 187–197). Image courtesy of Maria Antonietta De Matteis.
ER-Golgi membrane contact sites
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