- ERBIN links STAT3 and TGF-β with atopy
Lyons et al. show that STAT3 negatively regulates TGF-β signaling via ERBIN and that cell-intrinsic deregulation of TGF-β pathway activation promotes the IL-4/IL-4Rα/GATA3 axis to support atopic phenotypes in humans.
- Skap2 in integrin activation
Boras et al. demonstrate that Skap2, via interaction with WASp, regulates actin polymerization and binding of talin-1 and kindlin-3 to the β2 integrin, thereby being indispensable for β2 integrin activation and neutrophil recruitment.
- Extrasynaptic NMDA receptor pathological triad
Bading reviews many neurodegenerative diseases sharing heightened extrasynaptic NMDA receptor signaling, which causes a pathological triad with mitochondrial dysfunction, deregulation of transcription, and loss of dendritic structures and connectivity. Areas of therapeutic objects are defined to guide the design of novel neuroprotective combination therapies.
- Regulating TCR hyperresponsiveness in the ZAP-70 W131A mutant mouse
Hsu et al. show that a hypermorphic allele of Zap70, characterized by reduced autoinhibition, is associated with increased TCR signaling and triggers regulatory mechanisms by which negative selection and inhibitory receptors restrain TCR signaling to enforce T cell tolerance.
- Fh1 is essential for HSC functions
Guitart et al. performed an in vivo genetic dissection of the Krebs cycle enzyme fumarate hydratase (Fh1) in the hematopoietic system. Their investigations revealed multifaceted functions of Fh1 in the regulation of hematopoietic stem cell biology and leukemic transformation.
- 27-OH impairs neuronal glucose uptake
Ismail et al. show that 27-hydroxycholesterol, a peripheral cholesterol metabolite capable of passing the blood–brain barrier, reduces brain glucose uptake by upregulating the renin-angiotensin system and inhibiting GLUT4. This alteration affects memory processes and is likely to have implications on neurodegenerative diseases.
- Lipin-2 regulates NLRP3 inflammasome
Lordén et al. show that the phosphatidic acid phosphatase lipin-2 is a key regulator of the cellular machinery that generates IL-1β in macrophages. This work provides a molecular explanation for the development of the autoinflammatory disease known as Majeed syndrome.
- TRIM65 is required for MDA5 activation
Lang et al. identify E3 ligase TRIM65 as an essential component for the MDA-5 signaling pathway and provide solid evidence showing the importance of ubiquitination in MDA5 oligomerization and activation.
- NK cell survival during cell cycle
Natural killer (NK) cells eradicate virus-infected and transformed cells. Viant and colleagues describe the hierarchy of survival proteins and their apoptotic partners that govern NK cell survival. These data will inform approaches to harness NK cell activities in immunotherapies.