Volume 22 Issue 8, August 2020

Secretory proteins undergo multiple rounds of co- and post-translational quality control checks inside the cell, but how their integrity is maintained outside the cell is an emerging topic. A study establishes a model system to investigate how the extracellular proteome is protected and integrates its findings into existing immune pathways.

Cellular plasticity allows tumours to adapt to and overcome therapeutic challenges. A recent study uncovered the gene regulatory networks that govern cell states and phenotype switching in melanoma, opening up possibilities to therapeutically target cell states or phenotypic plasticity to render melanoma cells more vulnerable to treatment.

In this issue of Nature Cell Biology, Mercier et al. show that acute changes in membrane tension may be a physiological trigger for ESCRT assembly, which drives membrane scission, luminal vesicle budding, and a wide array of other membrane remodelling events throughout the cell.

There is increasing appreciation that many proteins self-aggregate in cells to form functional subcompartments, some of which exist as a separate liquid phase. A study now identifies the biophysical properties of AKAP95 protein condensates as critical for supporting cancer cell proliferation and RNA splicing.

Sato et al. demonstrate that IRF2, which negatively regulates interferon signalling, safeguards intestinal stem cells against non-infectious, sterile interferon stress by limiting their differentiation into secretory lineages.

Hsu et al. find that the protein kinase Akt acts as a co-adaptor in the clathrin coat complex and is needed in conjunction with ACAP1 to bind to cargo proteins to promote their recycling.

After lung injury, Kobayashi, Tata et al. find an intermediate cell state during the transition of alveolar type-2 into type-1 cells that is associated with senescence, controlled by TP53 and persists in fibrosis.

Mercier et al. demonstrate a role for endosomal membrane tension in modulating ESCRT-III polymerization, intra-lumenal vesicle formation and endosome trafficking.

Li et al. report that biophysical properties of AKAP95 protein condensates are essential to its physiological functions in RNA splicing and tumorigenesis.

Kumar et al. show that mammalian Atg8 proteins along with IRGM regulate the lysosomal system via mTOR and TFEB, respectively, in the response to pathogens.

Profiling phenotype switching in melanoma. Wouters et al. perform large-scale gene expression analysis in patient samples and identify transcriptional networks that modulate the intermediate cell state and ultimate mesenchymal switching in melanoma.

Dhamija et al. profile 3,412 nonstop mutations from 62 tumour entities and as proof of concept demonstrate that six such mutations cause degradation and loss of the tumour suppressor SMAD4.

Massou et al. combine cell stretching, super-resolution imaging and single-protein tracking to investigate integrin-based mechanosensing in live cells.