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Newly synthesised lysosomal proteins are sorted from other cargo on the secretory pathway for delivery to endolysosomal compartments. A study now shows that the Batten disease protein, CLN8, acts as a recycling receptor to sort soluble lysosomal enzymes for export from the endoplasmic reticulum to the Golgi.
Michel et al. report unique localization of non-canonical BAF to CTCF sites and promoters, which confers synthetic lethality in canonical BAF-perturbed synovial sarcoma and malignant rhabdoid tumour cells.
di Ronza et al. identify CLN8 as a cargo receptor for lysosomal enzymes required for their endoplasmic-reticulum-to-Golgi transport, linking Batten disease caused by CLN8 mutations to defects in organelle biogenesis.
Jung et al demonstrate that TMEM9 facilitates vacuolar-ATPase assembly to enhance vesicular acidification, thereby promoting activation of Wnt signalling and development of colorectal cancer.
Goddard et al review recent advances in our understanding of dormant tumour cells, highlight their cross-talk with immune responses, and elaborate therapeutic implications to treat metastatic malignancies.
Classical actin-dependent, integrin-mediated cell–matrix adhesions disassemble before mitotic rounding. Yet, to transmit positional information and facilitate daughter-cell separation, dividing cells maintain connections to the matrix. A previously unidentified class of actin-independent integrin adhesions may fulfil this task.
β-catenin regulates cell–cell adhesion and maintains stemness through Wnt signalling, but how these functions are mechanistically related is not fully understood. A study now identifies CRAD as the mechanistic link, providing insight into how dysregulation of epithelial adhesion contributes to Wnt-driven tumorigenesis.
The cancer-suppressive mechanisms underlying a tissue’s response to spontaneous oncogenic mutations during homeostasis are largely unknown. A study now explores how clonal expansion of epidermal stem cells with specific oncogenic mutations might be restricted by their elimination through enforced differentiation.
Lock et al. identify reticular adhesion complexes that maintain cell–extracellular-matrix attachments during cell division. Reticular adhesions transmit spatial memory between cell generations, mediated by αvβ5 integrin and PtdIns(4,5)P2.
Cigliola et al. show that β-cell loss activates insulin production in a small number of α-cells and that insulin and Hedgehog signalling actively maintain and enforce the α-cell fate.
Ying et al. show that oncogenic PI3K–AKT activation, through the suppression of SH3RF1, induces epidermal differentiation, inhibits progenitor self-renewal and prevents tumour initiation.
Jung et al. demonstrate that loss of CRAD impairs F-actin polymerization and disrupts the cadherin–catenin–actin complex, thereby hyperactivating Wnt signalling and promoting mucinous intestinal tumorigenesis.
Opposing kinesin-2 and dynein-1b motors drive IFT bidirectionally along microtubules. Using cryo-electron tomography, Jordan et al. uncover mechanisms of dynein-1 inhibition to promote unidirectional IFT to the ciliary tip.
Using time-lapse microscopy and transcriptome analysis of the post-implantation mouse embryo, Christodoulou et al. show that cavity fusion occurs through the formation and polarized resolution of multiple, multicellular three-dimensional rosettes.
Functional genetic screening of mice and other mammals is exceedingly challenging. A CRISPR-based mutagenesis screen in mice has successfully revealed amino acids vital for protein function of the DND1 gene, missense mutations of which lead to defects in primordial germ cell development.
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.
We are often asked about various aspects of the editor’s job, and most frequently about the editorial process after submission. Here, we outline what happens after a manuscript is submitted to the journal and clarify some misconceptions about the editorial process.
The intestinal crypt has become the prototype compartment to investigate adult stem cell biology, and the list of identified intestinal stem cell (ISC) markers is already extensive. A comprehensive study now uncovers an additional layer in ISC regulation by introducing long noncoding RNA lncGata6 to the stem cell repertoire.
Intra-tumour heterogeneity manifests both at the level of mutational burden, and at a functional level within genetically homogenous populations. A new modelling approach suggests stemness within colorectal tumours is defined by microenvironmental cues secreted from cancer-associated fibroblasts rather than cell-intrinsic properties.