Issues

Nan Yan studies the physiological function of innate immune signaling in the absence of pathogen infection.

Overholtzer discusses work from Bozkurt et al. showing that TRAIL signaling induces entosis in colon cancer cells.

Dustin previews work from Bessy, Candelas, and colleagues that describes the mechanisms that regulate how HSPCs polarize during interactions with specific stromal cells.

Casler and Lackner discuss work from the Schuldiner laboratory that identifies a novel mitochondria–nuclear ER contact site protein.

Carosi et al. examine a new type of ubiquitin-like protein modification that employs the ATG8 family of proteins.

Schneider and de Ruijter-Villani et al. demonstrate that two spindles assemble around the parental genomes in bovine zygotes even though, like human zygotes, they inherit centrioles from the sperm. The two independent microtubule arrays form by self-organization with only loosely connected centrosomes.

Labbé et al. demonstrate that the modified outer membrane carrier protein, MTCH2, is required for starvation-dependent mitochondrial hyperfusion in human cells and functions to stimulate mitochondrial fusion in a manner dependent on lysophosphatidic acid, linking mitochondrial dynamics to lipogenesis.

In modeling the bone marrow niche in vitro, Bessy et al. show that hematopoietic stem cells (HSPCs) polarize upon interaction with specific stromal cells. HSPCs adopt an elongated shape, pointing toward a focused anchorage site, close to which the centrosome localizes in response to SDF1.

Camillo et al. show that the LPHN2 receptor, upon activation by FLRT2 ligand, inhibits focal adhesion formation and promotes tight junction assembly in endothelial cells. Blood vessels of lphn2a null animals are hyperpermeable, and injected cancer cells extravasate more easily.

Kif18a mutant mice produce micronuclei following segregation of unaligned chromosomes but do not spontaneously form tumors. KIF18A KO cells form stable micronuclear envelopes around lagging chromosomes located near the spindle pole and outside the midzone. These data suggest stable micronuclei may not actively promote tumorigenesis.

A high-throughput screen uncovered a role for the uncharacterized protein, Ybr063c (Cnm1 [contact nucleus mitochondria 1]), as a molecular tether of the nucleus–mitochondria contact in yeast. Cnm1 on the nucleus mediates contact by interacting with Tom70 on mitochondria. Regulation of Cnm1 abundance by phosphatidylcholine enables coupling of phospholipid levels with contact extent.

Chio and Liu et al. show that the cytosolic domain of the Get2 membrane receptor plays an unforeseen role in remodeling and disassembling the targeting complex for nascent tail-anchored proteins. The new functions of Get2 are mediated by molecular recognition features in its disordered linker.

This study describes a unique monomethyl branched-chain fatty acid, C17iso, as the side chain of phospholipids to ensure endoplasmic reticulum integrity for lipid droplet growth in an intact organism, Caenorhabditis elegans.

Kelly et al. identify the hypervariable region of atlastins as a partially structured segment that in human atlastin-1 contributes to membrane tethering efficiency and is a site for distinct phosphorylation events, suggesting a mode of regulation by post-translational modification of the enzyme in cells.

Chen et al. provide a novel insight on how poly(PR) dipeptides from C9orf72 gene exert cytotoxicity. The alternate distribution of Arg facilitates multivalent protein–protein interactions with proteins harboring acidic motifs and disturbs their functions through entrapment in the phase-separated droplets.

Mitophagy is regulated by multiple interconnected pathways, which remain poorly understood in physiological settings. Shen et al. describe a mechanism of Pink1-dependent mitophagy utilizing Vps13D that acts in parallel to Parkin-mediated mitophagy during development.

Bock et al. show that the small Rho GTPase Rac1 is not essential for epithelial branching morphogenesis during kidney collecting duct development. However, Rac1 later maintains epithelial polarity, morphology, and function by Arp2/3-dependent cytoskeletal branching, which restricts actomyosin activity.

Nanba et al. demonstrate that the age-dependent decline of EGFR signaling impairs epidermal stem cell motility and reepithelialization through COL17A1 proteolysis. The resulting alteration of epidermal stem cell dynamics is involved in the decline of skin regenerative capacity with aging.

Ras GTPases are key membrane-associated elements of the EGFR-MAPK signaling pathway. Surve et al. demonstrate that endogenous KRAS and NRAS are predominantly localized to the plasma membrane and its tubular shaped protrusions and show that a small pool of surface EGFRs sustain signaling along the RAS-MAPK pathway, whereas internalized EGFRs do not significantly contribute to MAPK activity.

This paper shows that adjacent cells with similar genetic capabilities to change their own shape enter a tug of war that determines which cell shrinks and which expands. For a cell to contract, its neighbors must yield, requiring a nonlinear stress–strain response in the mechanism governing its physical properties.

Bozkurt et al. find that besides activating apoptosis, TRAIL signaling induces entosis in colon cancer cells through TRAIL receptors and structural presence but not catalytic activity of caspase-8. Moreover, they provide evidence for an association of TRAIL signaling, cell-in-cell structures, and clinical outcome in CRC.