Volume 21 Issue 6, June 2019

IRE1α is an endoplasmic reticulum (ER) transmembrane protein known for a crucial role in regulating the unfolding protein response. A study now shows that IRE1α interacts with the main ER Ca²⁺ channel InsP₃Rs and facilitates the transfer of Ca²⁺ from the ER into mitochondria, thus driving cellular metabolism.

Centromere identity must be maintained through multiple generations. A new study reveals a Constitutive Centromere-Associated Network (CCAN)-dependent retention of CENP-A, a key epigenetic mark for centromeres, in centromeres during DNA replication and a replication-dependent error correction to eliminate ectopic CENP-A in chromosome arms.

Embryonic stem cells derived from the inner cell mass can differentiate to all embryonic lineages of any adult cell type and to a limited extent to extra-embryonic tissues. A study now allows the generation of pig and human stem cells with enhanced differentiation potential towards all embryonic and extra-embryonic fates, one step closer to the totipotent state of the fertilized egg.

Wang et al. map early cardiopharyngeal development in the chordate model Ciona and show that FGF–MAPK signalling maintains multipotency and promotes pharyngeal muscle fate, whereas Tbx1/10-Dach specify second heart lineage identity.

Gao, Nowak-Imialek, Chen et al. generate porcine and human stem cells that possess expanded developmental potency for both embryonic and extra-embryonic cell lineages.

Lee et al. show that deleting Mettl3 from adult HSCs in mice leads to the accumulation of HSCs in the bone marrow and reduced reconstitution rates due to an inhibition of HSC differentiation.

Demarco et al. demonstrate that a block in mitochondrial fusion leads to a loss of male germline stem cells in Drosophila, a disruption of lipid homeostasis and activation of TOR signalling.

Grainger et al. demonstrate that, in zebrafish and human cells, EGFR-mediated phosphorylation of Fzd9b promotes internalization of the Wnt9a–Fzd9b–LRP signalosome and subsequent signal transduction.

Necroptosis drives arthritis. Polykratis et al. show that the deubiquitinating enzyme A20 inhibits inflammasome-dependent arthritis development by regulating macrophage necroptosis and this function depends on its ZnF7 ubiquitin binding domain.

Cleveland and colleagues report a DNA-replication-dependent error correction mechanism that acts in S phase to remove ectopically loaded CENP-A outside the centromeres, while retaining centromere-bound CENP-A.

Carreras-Sureda et al. uncover a non-canonical role for IRE1α as a scaffold that stabilizes InsP₃Rs at MAMs to control calcium uptake, fine-tunes ER–mitochondrial communication and regulates energy metabolism via AMPK.

Gutnick et al. design a light-sensitive small molecule, zapalog, which reversibly dimerizes any two proteins. Tethering mitochondria to active kinesin motors uncovers distinct modes of mitochondrial motility in axons.

Coppé and colleagues design a peptide phosphorylation-screening system that simultaneously measures the enzymatic activity of multiple kinases, identifying mechanisms of therapy resistance and druggable targets in colorectal cancer and melanoma.