Nature Reviews Molecular Cell Biology

Phillips, Melissa J.; Voeltz, Gia K.

doi: 10.1038/nrm.2015.8pmid: 26627931

The endoplasmic reticulum (ER) forms tight membrane contact sites (MCSs) with several organelles in animal cells and yeast. The function of MCSs between the ER and mitochondria and endosomes are summarized in this Review. Electron microscopy studies reveal that although MCSs are less than 30 nm apart, the membranes do not fuse and each organelle maintains its identity. Ribosomes are excluded from the ER membrane at MCSs, and the distance between the ER and other membranes is close enough to suggest that the two organelles are tethered together by other proteins located on apposing membranes. Live-cell fluorescence microscopy reveals that ER-organelle MCSs can remain stable while both organelles traffic through the cell on the cytoskeleton. Recently identified factors have been shown to regulate organelle trafficking through MCS formation. ER–organelle MCSs regulate the lipid environment of the organelle membrane apposed to the ER. Lipid-synthesis proteins on the ER can modify lipids on the membrane of another organelle or on protein complexes. ER MCS may also transfer lipids between membranes. ER–organelle MCSs are sites of dynamic Ca2+ crosstalk. Organelles can sequester Ca2+ released from the ER, which can regulate processes in these organelles. Additionally, ER Ca2+ release may regulate protein complexes at ER MCS. Mitochondria and endosomes undergo fission and fusion to, respectively, maintain their integrity and properly sort signalling receptors in the cell. ER–organelle MCSs define the position of fission for both mitochondria and endosomes, and the ER could have a variety of roles at those specific MCSs that are destined for fission.

Strzyz, Paulina

doi: 10.1038/nrm.2015.26pmid: 26695193

Centrosomes can nucleate not only microtubules but also actin filaments, in a process dependent on the actin-related protein 2/3 complex and WASH.

Nishikura, Kazuko

doi: 10.1038/nrm.2015.4pmid: 26648264

A-to-I RNA editing is catalysed by adenosine deaminases acting on RNA (ADARs). Three mammalian ADAR genes (ADAR1, ADAR2 and ADAR3) with common functional domains have been identified. Protein-coding sequences of a limited number of genes, such as glutamate receptor GRIA2 and serotonin receptor HTR2C, are edited, resulting in dramatic alterations of protein functions. Deficiencies in A-to-I RNA editing cause human diseases and pathophysiology. Genome-wide screening has identified numerous A-to-I editing sites in inverted Alu repeats located in non-coding regions of mRNAs. Alu editing in these transcripts is likely to affect many cellular processes. The biogenesis and function of certain miRNAs is regulated by editing of the primary miRNAs (pri-miRNAs). ADAR1 forms a complex with Dicer to promote the efficacy of miRNA processing and RNA interference (RNAi) in developing embryos.