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2019 marks twenty years since the launch of Nature Cell Biology. To celebrate our 20th anniversary we present a Focus of specially commissioned Review and Perspective articles that discuss topics across the diverse areas covered by the journal. These pieces are accompanied by a Collection of research articles published in Nature Cell Biology over the last two decades. Although they are not intended to be comprehensive, these commissioned pieces and research articles highlight the rich history and diverse scope of the journal.
Lyden and colleagues use asymmetric flow field-flow fractionation to classify nanoparticles derived from cell lines and human samples, including previously uncharacterized large, Exo-L and small, Exo-S, exosome subsets.
Li and colleagues develop a CRISPR–Cas9-based screen strategy that combines base editing and haploid embryonic stem cell technologies to identify amino acids critical for protein function in mice.
Glück et al. find that the DNA-sensing component cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments produced in senescent cells leading to STING-mediated production of SASPs, which promotes paracrine senescence.
Integrins and talin are parts of a ‘molecular clutch’ that mechanically links the actin cytoskeleton to the extracellular matrix. Elosegui-Artola et al. now reveal a tunable rigidity threshold, above which talin unfolds to mediate force transduction.
Medina, Ballabio and colleagues report that calcium release from the lysosome stimulates calcineurin, which dephosphorylates and activates TFEB. These findings reveal a central role for calcium signalling in autophagy and lysosome homeostasis.
Vale and colleagues report the distinct abilities of different tubulin isotypes and post-translational modifications to regulate different microtubule motors and their properties.
A property of oncogene-induced senescence (OIS) is the induction of a secretory phenotype, termed the senescence-associated secretome (SASP). Gil and colleagues now provide evidence that senescence can be transmitted in a paracrine manner, by showing that induction of the SASP in cells undergoing OIS by inflammasome-mediated interleukin-1 signalling can promote senescence of normal neighbouring cells.
D’Adda di Fagagna and colleagues observe that, after genotoxic treatment of cells and mice, unrepaired DNA-damage foci and DNA-damage signalling persist at telomeres. They show that introducing the telomeric protein TRF2 near a double-strand break elsewhere on the chromosomes prevents repair. Unrepaired foci are also observed at telomeres of ageing animals, suggesting a role for TRF2 in senescence establishment.
In mammalian cells, long-range vesicular transport is thought to occur via microtubule tracks. However, Schuh reports the existence of an actin-based pathway for long-range trafficking in mouse oocytes by showing that Rab11a-positive vesicles are decorated with actin-nucleating formin proteins. She finds that these proteins assemble actin networks that guide vesicles to the cell surface.
A molecular mechanism that links the mTOR and autophagy pathways is now revealed. Depending on nutrient availability, the AMPK and mTOR kinases differentially phosphorylate the autophagy-initiating kinase Ulk1 to regulate its activity.
53BP1 is marker of double-strand breaks and accumulates in nuclear foci. These foci are shown to accumulate in G1 at lesions generated by replication stress and may shield lesions from erosion.
As focal adhesions mature in response to mechanical tension and contractility, their protein composition changes. A proteomics analysis of focal adhesions following changes in myosin II activity highlights a role for the Rac guanine exchange factor β-Pix in promoting cell migration and nascent focal adhesion turnover, thereby preventing their maturation.
Impaired turnover of the autophagy substrate p62 leads to liver injury. p62 inhibits the ubiquitin ligase Keap1, leading to stabilization of the transcription factor Nrf2. High levels of p62 in autophagy deficient animals leads to unusually high expression of Nrf2 targets genes and results in liver injury.
The E3 ubiquitin ligase Parkin mediates the clearance of depolarized mitochondria through the autophagy pathway. PINK1 kinase activity is required for Parkin translocation to depolarized mitochondria where Parkin generates polyubiquitin chains on the voltage-dependent anion channel (VDAC1) to recruit the autophagic adaptor p62/SQSTM1.
Persistent DNA damage activation and oncogene-induced senescence stimulate secretion of the inflammatory cytokine IL-6, which is mediated by the damage-response pathway including ATM, NBS1 and CHK2. Tumours with an activated DNA damage response show elevated IL-6 and invasiveness.
Exosome biogenesis is poorly understood. The small GTPases Rab27a and Rab27b and their effectors, Slp4 and Slac2b, control exosome secretion at different steps by regulating the peripheral localization, retention and docking of exosomal precursors, the multivesicular endosomes.