December 2017 | Volume 216, No. 12
News
Editorial
In Focus
UNC-45a helps cells manage their stress levelsThe chaperone UNC-45a helps non-muscle myosin II fold and assemble into contractile stress fibers.
People & Ideas
Nasser Rusan: Scoping out centrosomesRusan investigates how centrosomes control cell behavior and differentiation during development.
Reviews
Reviews
Regulation and dysregulation of axon infrastructure by myelinating gliaPan and Chan discuss the role of myelinating glia in axonal development and the impact of demyelination on axon degeneration.
Proteinopathies and OXPHOS dysfunction in neurodegenerative diseasesKawamata and Manfredi review proposed mechanisms of how the accumulation of misfolded proteins in neurodegenerative diseases causes mitochondrial dysfunction.
How to rewire the host cell: A home improvement guide for intracellular bacteriaCornejo, Schlaermann, and Mukherjee discuss how intracellular bacteria usurp host cells and what cell biologists can learn from these methods.
Research Articles
Reports
Chromosome biorientation and APC activity remain uncoupled in oocytes with reduced volumeLane 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.
Prepatterning by RhoGEFs governs Rho GTPase spatiotemporal dynamics during wound repairDuring 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.
Membrane curvature directs the localization of Cdc42p to novel foci required for cell–cell fusionThe 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.
An apicosome initiates self-organizing morphogenesis of human pluripotent stem cellsEstablishment 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.
Articles
RECQ-like helicases Sgs1 and BLM regulate R-loop–associated genome instabilityChang 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.
Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factorsMoriel-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.
Selective aggregation of the splicing factor Hsh155 suppresses splicing upon genotoxic stressAlterations 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.
SUMOylation of human septins is critical for septin filament bundling and cytokinesisYeast 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.
UNC-45a promotes myosin folding and stress fiber assemblyHow 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.
ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formationNeutrophils 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 cellsCancer 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 responsesType 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.
Receptor-mediated Drp1 oligomerization on endoplasmic reticulumAssembly 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 carriersChen 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.
cTAGE5 deletion in pancreatic β cells impairs proinsulin trafficking and insulin biogenesis in miceIn 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.
Regulation of NOTCH signaling by RAB7 and RAB8 requires carboxyl methylation by ICMTSome 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.
A Ragulator–BORC interaction controls lysosome positioning in response to amino acid availabilityAmino 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.
LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioningFunctions 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.
PtdIns3P controls mTORC1 signaling through lysosomal positioningmTORC1 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 parasite Toxoplasma sequesters diverse Rab host vesicles within an intravacuolar networkThe 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.
Receptor tyrosine kinase activation of RhoA is mediated by AKT phosphorylation of DLC1A 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.
An excitable Rho GTPase signaling network generates dynamic subcellular contraction patternsA 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.
The α6β4 integrin promotes resistance to ferroptosisLipid 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.
Ectopic expression of Pax4 in pancreatic δ cells results in β-like cell neogenesisDiabetes 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.
Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrainNeuroblasts 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.
Rac3 regulates breast cancer invasion and metastasis by controlling adhesion and matrix degradationDonnelly 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.
Tools
New tools for “hot-wiring” clathrin-mediated endocytosis with temporal and spatial precisionWood 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.
Commentary
Spotlights
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.
Wu discusses a study by Graessl et al. that describes a Rho GTPase signaling network that combines positive and negative feedback to regulate subcellular contraction patterns.