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Multicellular fungi have septal pores that allow cytoplasmic exchange between adjacent cells; cell wounding and other stress conditions induce septal pore closure. Here, Mamun et al. determine the subcellular localization of hundreds of uncharacterized proteins in a multicellular fungus, identifying 62 proteins associated with the septum. Of these, 23 proteins are involved in septal pore plugging upon hyphal wounding.

New mutations and genes associated with malformations of cortical development keep being identified, yet there is little known about the underlying cellular mechanisms controlling these impairments. Here, authors generate and characterize a heterozygous TUBG1 knock-in mouse model bearing one of these known mutations and show that TUBG1 mutation leads to the miss-positioning of neurons in the cortical wall due to migration, because of defective microtubules dynamics, and not proliferation defects during corticogenesis.

Higher-order TCRs have been postulated to maintain high antigen sensitivity and trigger signaling. Huppa and colleagues use various investigative techniques and find exclusively monomeric TCR–CD3 complexes that drive the recognition of antigenic pMHC.

Ependymal cell cilia regulate cerebrospinal fluid flow through the cerebral ventricles. Here the authors show that the metabolic peptide melanin-concentrating hormone (MCH) increases cilia beat frequency in the third ventricle, and a lack of the MCH receptor increases ventricle size.

Fiolopodia are involved in cell migration and their attachment to the ECM is mediated by integrin receptors. Here the authors show that myosin X induced filipodia adhesion to fibronectin requires activity of myosin IIA at the filopodium base and formin at the tip to support force transmission through the actin core.

A highly selective inhibitor of the DCLK1/2 kinases is used to uncover the consequences of DCLK1 inhibition on viability, phosphosignaling and the transcriptome in patient-derived organoid models of pancreatic ductal adenocarcinoma.

Surface diffusion of AMPA receptors, from extra-synaptic to synaptic sites at the plasma membrane, is essential for full long-term potentiation in hippocampal neurons and for fear conditioning in living mice.

The interaction between focal adhesion proteins vinculin and talin is stimulated by mechanical stretching. Here the authors reconstitute actomyosin-dependent stretching of talin in vitro, and show that the resulting activation of vinculin reinforces anchoring of the adhesion complex to actin.

Invasive extravillous trophoblast cells are a key feature of placentation and successful pregnancy. Here, the authors identify transcription factors and regulatory mechanisms critical for extravillous trophoblast cell lineage development.

Caveolae are mechanosensors and mutations of their coat proteins are implicated in muscle disorders, but molecular mechanisms are unclear. Here, the authors show that caveolae can regulate IL6/STAT3 signaling in muscle cells under stress, and that dystrophy related Cav3 mutant myotubes have reduced caveolae and upregulated IL6 signaling.

Lateral diffusion of receptors between synaptic and extrasynaptic sites is known to mediate plasticity. Hausrat et al. show that diffusion of α5-containing GABA_Areceptors is controlled by phosphorylation of the extrasynaptic anchoring protein Radixin, and reveal a role for Radixin in learning and memory.

RNA-interacting proteome can be identified by RNA affinity purification followed by mass spectrometry. Here the authors developed a different RNA-centric technology that combines high-throughput immunoprecipitation of RNA binding proteins and luciferase-based detection of their interaction with the RNA.

Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

Inhibition of immune cell–derived acetylcholine synthesis or of its signaling via CHRNA2 in beige adipocytes reduces thermogenesis and exacerbates diet-induced obesity, suggesting a new mode of immuno–fat communication in energy metabolism.

The polarisome is a dynamic protein complex that nucleates F-actin for polarized yeast growth, but its regulation is unclear. Here, the authors report that the polarisome protein Aip5 undergoes Spa2-mediated phase separation in physiological and stress conditions, potentially for regulating actin assembly.

There is growing evidence that autophagy might serve specialized functions in neurons besides its role in protein homeostasis. In this study, authors demonstrate that axonal retrograde transport of BDNF/TrkB in neuronal amphisomes is involved in plasticity-relevant local signaling at presynaptic boutons and that SIPA1L2, a member of the SIPA1L family of neuronal RapGAPs, associates via LC3b to TrkB-containing amphisomes to regulate its motility and signaling at the axon terminals

PD-L1 on tumor cells exerts an important dampening effect on T cells via their expression of PD-1. Miller and colleagues find that PD-L1 ‘back-signaling’ into T cells and macrophages can also dampen immune responses within the tumor microenvironment.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Polycystin-2 (PC2) is an ion channel commonly found mutated in autosomal dominant polycystic kidney disease. Here Arhatte et al. identify transmembrane protein 33 (TMEM33) as a regulator of PC2 function at the endoplasmic reticulum, and find that deletion of TMEM33 protects mice from acute kidney injury.

Phosphatidylserine and its receptors are associated with cell-cell fusion. Here, the authors show the phosphatidylserine receptor stabilin-2 is expressed by muscle cells and plays a vital role in myoblast fusion and post-injury muscle regeneration in mice.

During cell division, a cytoplasmic bridge—the midbody—forms between the nascent daughter cells, but it has been unclear under which conditions this is retained by a daughter cell or released. Now, Ettinger and colleagues show that midbody-release occurs more frequently in stem cells compared with cancer cells.

Many intracellular pathogens mimic extracellular matrix motifs to specifically interact with the host membrane which may influences virus particle uptake. Here authors use single molecule tension sensors to reveal the minimal forces exerted on single virus particles and demonstrate that the uptake forces scale with the adhesion energy.

Asymmetric spindle positioning in female mouse meiosis depends on the assembly of actin networks. Here, Chaigne et al. show by theoretical modelling and artificial manipulation of the oocyte cortex that a narrow stiffness regime is required to correctly position the spindle during meiosis I in the mouse oocyte.

Mechanosensitive channels are required to sense cell swelling in response to osmotic shock. Nakayamaet al.report that Msy1 and Msy2 are the fission yeast homologues of the bacterial mechanosensitive channel MscS, and are required for regulating intracellular calcium in response to cell swelling.

How the mitotic spindle is positioned in the centre of the cell during the first mitotic division is not clear. Here Chaigne et al.show that the pronucleus coarsely centres using F-actin/Myosin-Vb dynamics, and the metaphase plate is finely centred by an F-actin cage influenced by high cortical tension.

Molecular and oscillations are common in biology, but periodic cell migrations have not been observed. Fraleyet al. report regular, periodic migrations of cells along tracks generated inside 3D matrices, and show that these 1D oscillations are controlled by zyxin and its binding partners α-actinin and p130Cas.

The development of hydrogel composites with enhanced moisture-capturing properties is hindered by our limited understanding behind their moisture-capture properties. Here, the authors develop and validate a theoretical description that bridges this knowledge gap for a wide range of synthesized and characterized hydrogel-salt composites.

A photoswitch based on a bacterial phytochrome enables optogenetic manipulations using red light.

The radioactive element uranium tends to accumulate in wetland soils in the insoluble and immobile tetravalent form. Wang et al. show that uranium(IV) can associate with highly mobile organic- and iron(II)-bearing colloids and that its mobility in organic-rich environments may be severely underestimated.

Microtubules vary their length by gaining and shedding tubulin dimers dynamically at both ends. But evidence now suggests that dimers may also be incorporated into the middle of the shaft—calling into question existing models of growth dynamics.

Polarized photoluminescence spectra of europium-doped nanorods can be used to measure the local shear rate profile of a liquid in microfluidic channels.

The adaptability of the plant Arabidopsis thaliana to different temperatures is regulated by the ability of its ELF3 protein to undergo liquid–liquid phase separation, in a manner that is dependent on the protein’s prion-like domain.

Auxiliary AMPA receptor subunits can affect gating and surface mobility. Here the authors show that Shisa6 traps AMPA receptors at postsynaptic sites via PSD-95, and keeps them in an activated state in the presence of glutamate, preventing full desensitization and consequently synaptic depression.

Complex genomic alterations segregate melanoma into different molecular subsets, but for most subsets it is unclear whether they drive a distinct clinical behaviour. Here, the authors use gene-expression data from melanoma patients to search for outlier genes that correlate with survival and identify that MTSS1 is associated with metastasis.

The human serotonin transporter (SERT) mediates the uptake of neurotransmitters to terminate neuronal signalling. Here the authors use single-molecule imaging to get insight into the molecular origin of SERT oligomerization and their pre-set stoichiometry at the plasma membrane.

Epigenetic regulators are promising targets for cancer drugs, as they can modulate a broad range of transcriptional networks simultaneously. Here, the authors identify an inhibitor of Jumonji-family histone demethylases and show that it selectively kills cancer cells in mouse tumour models.

Mutations inGPSM2cause a rare disease characterized by deafness and brain abnormalities. Here the authors show that Gpsm2 forms a molecular complex with a heterotrimeric G-protein subunit, whirlin and a myosin motor to regulate actin dynamics in neurons and auditory hair cell stereocilia.

Cell-based screening assays allow functional testing of chemicals but do not mimic the in vivosituation well. Here, the authors report a method for the discovery of secreted cytoprotective factors in mice and use it to demonstrate that the hormone ghrelin protects cardiac muscle from ischaemic damage.

CKK domain containing CAMSAP/Patronins recognise and regulate microtubule (MT) minus end dynamics. Here the authors compare cryo-EM structures of MT-bound human CKK and Naegleria gruberi CKK which lacks minus-end binding preference, finding NgCKK has a different interaction with, and inability to remodel, its MT binding site, shedding light on the CAMSAP/Patronin end binding mechanism.