Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Systematic analyses of mechanical signalling in cells on surfaces of different rigidities reveal a tunable rigidity threshold above which talin unfolds to mediate force transduction.
Many biological processes are influenced by the mechanical rigidity of surrounding tissues. Now, a combination of experiments and mathematical modelling has been used to describe the precise molecular and physical mechanism by which cells sense and respond to the mechanical properties of their extracellular environment through integrin-based adhesions.
Contact sites between the endoplasmic reticulum and the plasma membrane mediate receptor signalling. How this function is controlled physically and functionally is poorly understood. Extended synaptotagmins are now shown to shuttle the lipid metabolite diacylglycerol from the plasma membrane to the endoplasmic reticulum in receptor-stimulated cells.
Wnt/β-catenin signalling is an important regulator of liver development, zonation and regeneration. The cell surface complex RSPO–LGR4/5–ZNF3/RNF43 is now shown to direct Wnt/β-catenin signalling in orchestrating the division of the liver into functionally distinct metabolic zones, providing insights into the mechanisms that influence organ development and regeneration.
The liver is the most common metastatic route of pancreatic cancer. Early recruitment of granulin-secreting inflammatory monocytes to the liver is now shown to reprogram hepatic stellate cells into myofibroblasts that modulate the liver microenvironment to support the growth of metastasizing tumour cells.
Tchorz and colleagues identify a role for the RSPO–LGR4/5–ZNRF3/RNF43 module as master regulator of Wnt/β-catenin-mediated metabolic liver zonation and hepatic growth/size control during development, homeostasis and regeneration.
Rudolph and colleagues identify Per2 as a negative regulator of lymphoid-biased haematopoietic stem cells, and show that it reduces cell maintenance and function in response to DNA damage and ageing.
Gundersen and colleagues report that FAK, talin and PIPKIγ maintain the active conformation of integrin that is internalized in Rab11 recycling endosomes, to polarize focal adhesion assembly for directed cell migration.
Saheki and colleagues show that extended synaptotagmins (E-Syts), ER proteins that function as tethers to the plasma membrane, can transfer lipids between bilayers in a Ca2+- and SMP-domain-dependent manner, thus regulating plasma membrane lipid homeostasis.
Mendoza and colleagues provide insights into the specificity of the NoCut checkpoint, showing that although different types of chromosomal defects delay cytokinetic abscission, only after replication stress does this prevent DNA damage.
Dai and colleagues reveal that proteotoxic stress causes JNK-mediated disintegration of the mTORC1 complexes, whereas heat shock factor 1 (HSF1) counteracts this response to promote stress resistance and growth.
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.
Nielsen et al. show that granulin is secreted by metastasis-associated macrophages to promote pancreatic cancer metastasis. Granulin activates hepatic stellate cells, which secrete periostin, thereby resulting in a fibrotic, pro-metastatic liver milieu.
Li et al. show that the c-Myc-dependent splicing switch from ketohexokinase-C (KHK-C) to KHK-A activates phosphoribosyl pyrophosphate synthetase 1 (PRPS1), resulting in enhanced de novo nucleic acid synthesis and hepatocellular carcinoma formation.
Lien et al. show that oncogenic PI(3)K/Akt signalling stimulates glutathione (GSH) synthesis by activation of the transcription factor Nrf2 and regulation of GSH biosynthesis genes in breast cancer.
