People & Ideas
Romero-Morales et al. preview work from the Taniguchi et al. describing the role of a new structure, the apicosome, in lumenogenesis.
Colaço and Jäättelä discuss studies from Pu et al. and Filipek et al. that identify Ragulator as a dynamic regulator of lysosomal trafficking.
Pan and Chan discuss the role of myelinating glia in axonal development and the impact of demyelination on axon degeneration.
Kawamata and Manfredi review proposed mechanisms of how the accumulation of misfolded proteins in neurodegenerative diseases causes mitochondrial dysfunction.
Cornejo, Schlaermann, and Mukherjee discuss how intracellular bacteria usurp host cells and what cell biologists can learn from these methods.
Lane and Jones use serial bisection of mouse oocytes to analyze the influence of cytoplasmic volume on spindle assembly checkpoint function. Volume reduction promotes inhibition of APC but cannot prevent chromosome segregation errors at anaphase.
During wound repair, Rho GTPases form dynamic spatial and temporal patterns surrounding the wound and coordinate the cytoskeletal response. Nakamura et al. show that Rho GTPase arrays form in response to prepatterning by RhoGEFs, which depends on annexin B9.
The Rho–GTPase Cdc42p promotes yeast fusion during mating. Smith et al. find that Cdc42p forms a novel focus at the center of the zone of cell fusion that is required for fusion. Formation of the focus depends on fusion proteins and is sensitive to the curvature of the zone of cell fusion.
Establishment of apicobasal polarity is critical for the lumenal epiblast-like morphogenesis of human pluripotent stem cells (hPSC). Taniguchi et al. show that apical polarization begins on the interior of single hPSC, through dynamic formation of a highly organized, apically charged perinuclear complex called the apicosome.
Chang et al. link the RECQ-like helicase BLM and its yeast orthologue Sgs1 to preventing DNA damage caused by the accumulation of DNA:RNA hybrid structures called R-loops. This adds to a growing family of helicases implicated in R-loop resolution.
Moriel-Carretero et al. show that the Fanconi anemia proteins FANCI and FANCD2 associate with the splicing factor SF3B1 and that DNA replication stress induces the FANCI-dependent release of SF3B1 from nuclear speckles. FANCI and FANCD2 prevent accumulation of postcatalytic intron lariats, suggesting that they help coordinate DNA replication and transcription.
Alterations of the transcriptome and proteome enable stress recovery, but coordination of these events under stress is only partly understood. Mathew et al. report that under stress, an RNA splicing complex disassembles and the splicing factor Hsh155 moves to protein aggregates, coinciding with a drop in splicing and concomitant repression of ribosome production.
Yeast septins were among the first proteins reported to be SUMOylated, but the impact of this modification on septin function is unclear. Ribet et al. show that septins are SUMOylated in humans and that SUMOylation is critical for septin bundle formation and septin function in cell division.
How nonmuscle myosin II is recruited to contractile actomyosin bundles or stress fibers and assembled into functional bipolar filaments is unclear. Lehtimäki et al. show that UNC-45a functions as a myosin chaperone that contributes to the assembly of functional stress fibers.
Neutrophils can release their genomic DNA as extracellular traps (NETs), which ensnare bacteria and limit their replication. Stojkov et al. find that modulation of cytoskeletal dynamics by reactive oxygen species and glutathionylation controls the degranulation and release of mitochondrial DNA required for NET formation.
BAG3 directly stabilizes Hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells
Cancer cells frequently exhibit aerobic glycolysis, known as the Warburg effect. An et al. identify a novel RNA regulatory activity of BAG3, a protein implicated in various cancers. BAG3 enhances posttranscriptionally the expression of Hexokinase 2, the first enzyme involved in glycolysis, and it reprograms glucose metabolism by pancreatic cancer cells.
Type I interferon enhances necroptosis of Salmonella Typhimurium–infected macrophages by impairing antioxidative stress responses
Type I interferon (IFN-I) triggers necroptosis in macrophages infected with S. Typhimurium by an unclear mechanism. Hos et al. now demonstrate that RIP3 enhances the interaction of Nrf2 with Pgam5 in response to IFN-I signaling in S. Typhimurium–infected macrophages, which abates Nrf2-dependent cytoprotective pathways and increases cell death.
Assembly of the dynamin GTPase Drp1 into constriction-competent oligomers is a key event in mitochondrial division. Here, Ji et al. show that Drp1 oligomerization can occur on endoplasmic reticulum through an ER-bound population of the tail-anchored protein Mff.
Segregation in the Golgi complex precedes export of endolysosomal proteins in distinct transport carriers
Chen et al. present evidence that two sets of newly synthesized endolysosomal proteins segregate in the Golgi complex before their export in two distinct populations of transport carriers, by mechanisms that are respectively dependent or independent of sorting signal–adaptor interactions.
In this study, Fan et al. show that cTAGE5 interacts with the v-SNARE Sec22b to regulate proinsulin processing and COPII-dependent trafficking from the ER to the Golgi, thereby influencing glucose tolerance.
Some prenylated proteins such as RAS require carboxyl methylation by ICMT for proper association with cellular membranes. Court et al. show that RAB7 and RAB8 are among these proteins and that by affecting vesicular transport, these GTPases regulate NOTCH signaling in an ICMT-dependent fashion.
Amino acid depletion turns off Ragulator/mTORC1 signaling and causes juxtanuclear clustering of lysosomes, but the mechanisms involved are unclear. Pu et al. show that amino acid depletion enhances a negative regulatory interaction of the Ragulator complex with BORC, inhibiting lysosome transport and causing their juxtanuclear clustering.
Functions of lysosomes are tightly associated with their position within the cell. Filipek et al. identify the EGF-dependent LAMTOR/Ragulator-BORC interaction as a negative regulator of Arl8b lysosomal recruitment that triggers plus-end directed lysosome movement.
mTORC1 is activated by lysosome positioning and by amino acid–induced phosphatidylinositol 3-phosphate (PtdIns3P). Hong et al. show that amino acids stimulate recruitment of the PtdIns3P-binding protein FYCO1 to lysosomes and promote contacts between FYCO1 lysosomes and ER that contains the PtdIns3P effector Protrudin, mediating lysosome translocation and facilitating mTORC1 activation.
The human pathogen Toxoplasma sequesters host vesicles filled with nutrients into its parasitophorous vacuole. Romano et al. now identify parasite effectors located at an intravacuolar membrane network that control internalization and degradation of these vesicles and cargo release within the vacuole.
A new common mechanism for increasing RhoA-GTP is identified in Tripathi et al. The increased RhoA-GTP results from signaling mechanisms that phosphorylate and attenuate the DLC1 tumor suppressor, which encodes RhoGAP. The potentially reversible nature of this attenuation may have therapeutic relevance in cancer.
A signaling network is revealed that combines positive and negative feedback to control the activity of the small GTPase Rho in adherent cells. This network generates spontaneous pulses of Rho activity and actomyosin contraction that are modulated by extracellular elasticity.
Lipid peroxidation in the plasma membrane can cause ferroptosis, a form of regulated necrosis. Brown et al. show that matrix detachment can induce ferroptosis, and the α6β4 integrin impedes that process by suppressing expression of the proferroptotic enzyme ACSL4.
Diabetes can result from the loss or dysfunction of insulin-producing δ cells. Druelle et al. find that ectopic expression of the pancreatic beta cell master gene Pax4 in somatostatin-expressing δ cells triggers an endocrine cell neogenesis process. Importantly, the beta-like cells thereby generated are functional and can partly reverse the consequences of chemically induced diabetes.
Neuroblasts born postnatally in the ventricular–subventricular zone migrate long distances via the rostral migratory stream (RMS) to the olfactory bulb. Nakamuta et al. show that DOCK7 drives tangential migration of neuroblasts in the RMS by controlling both leading process extension and somal translocation through Rac-dependent and myosin phosphatase–RhoA–interacting protein-dependent pathways, respectively.
Donnelly et al. demonstrate that invasion and metastasis of breast cancer cells depend on Rac3-GTPase signaling at invadopodia. Using a novel FRET biosensor, they show that Rac3 activity is regulated by the spatial organization of two RhoGEFs. Rac3 balances the proteolytic and adhesive activities necessary for invasion by integrating extracellular matrix adhesion and MT1-MMP presentation at invadopodia.
Wood et al. have developed inducible chemical and optogenetic systems for triggering clathrin-mediated endocytosis using minimal clathrin-binding domains. Bypassing regulatory steps in vesicle creation will enable a better understanding of the factors required for vesicle initiation and processing, which the authors use to define how clathrin functionally interacts with its adaptor AP2.