Cell Research最新文献

Equilibrioception (sensing of balance) is essential for mammals to perceive and navigate the three-dimensional world. A rapid mechanoelectrical transduction (MET) response in vestibular hair cells is crucial for detecting position and motion. Here, we identify the G protein-coupled receptor (GPCR) LPHN2/ADGRL2, expressed on the apical membrane of utricular hair cells, as essential for maintaining normal balance. Loss of LPHN2 specifically in hair cells impaired both balance behavior and the MET response in mice. Functional analyses using hair-cell-specific Lphn2-knockout mice and an LPHN2-specific inhibitor suggest that LPHN2 regulates tip-link-independent MET currents at the apical surface of utricular hair cells. Mechanistic studies in a heterologous system show that LPHN2 converts force stimuli into increased open probability of transmembrane channel-like protein 1 (TMC1). LPHN2-mediated force sensation triggers glutamate release and calcium signaling in utricular hair cells. Importantly, reintroducing LPHN2 into the hair cells of Lphn2-deficient mice restores vestibular function and MET response. Our data reveal that a mechanosensitive GPCR is required for equilibrioception.

The aged immune system contributes to systemic aging, serving as a driver of morbidity and mortality in the elderly. In a recent Cell Research paper, Wang et al. identified both resilient and dysfunctional subsets of old hematopoietic stem cells (HSCs), of which selective reduction of dysfunctional old HSCs ameliorates aging phenotypes and extends lifespan in mice.

Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear. Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it Raptin. Raptin release is timed by the circuit from vasopressin-expressing neurons in the suprachiasmatic nucleus to RCN2-positive neurons in the paraventricular nucleus. Raptin levels peak during sleep, which is blunted by sleep deficiency. Raptin binds to glutamate metabotropic receptor 3 (GRM3) in neurons of the hypothalamus and stomach to inhibit appetite and gastric emptying, respectively. Raptin-GRM3 signaling mediates anorexigenic effects via PI3K-AKT signaling. Of note, we verify the connections between deficiencies in the sleeping state, impaired Raptin release, and obesity in patients with sleep deficiency. Moreover, humans carrying an RCN2 nonsense variant present with night eating syndrome and obesity. These data define a unique hormone that suppresses food intake and prevents obesity.

Correction to: Cell Research https://doi.org/10.1038/s41422-024-01064-6, published online 26 December 2024

A recent study by Liao et al. reveals a sophisticated mechanism in rice where the transcription factor bHLH25 senses H₂O₂, orchestrating two independent defense pathways: lignin biosynthesis for physical reinforcement and phytoalexin production for antimicrobial action.

Although small nucleolar RNAs (snoRNAs) are well-known for guiding 2′-O-methylation and pseudouridine modification on ribosomal RNAs and small nuclear RNAs, their additional functions have remained largely undefined. Liu and colleagues developed snoKARR-seq to map transcriptome-wide snoRNA targets, and discovered an unexpected role of snoRNA: SNORA73 simultaneously binds to the target mRNA and the 7SL RNA of the signal recognition particle to form ternary interactions that facilitate the secretion of the encoded protein.

Antigen-based systems offer highly specific binding and customizability, broadening their application to various fields of cell biology. In a recent issue of Nature, Kalogriopoulos et al. design antigen-sensing G-protein-coupled receptors that exhibit programmable responses spanning exogenous gene expression, G-protein signaling, and receptor activation.