How to remake a fibroblast into a neural stem cell

In this issue of Cell Stem Cell and in a recent issue of PNAS, Thier et?al. (2012), Han et?al. (2012), and Lujan et?al. (2012) report the derivation of multipotent neural stem/progenitor cells from cultured mouse fibroblasts using distinct reprograming approaches.     

Finally, Polyubiquitinated PCNA Gets Recognized

Studies from Ciccia et?al. (2012) and Yuan et?al. (2012) in this issue of Molecular Cell, together with Weston et?al. (2012), reveal that the translocase ZRANB3/AH2 can recognize K63-linked polyubiquitinated PCNA and plays an important role in restarting stalled replication forks.     

Lymphocyte choriomeningitis virus plays hide-and-seek with type 1 interferon

In this issue, Macal et?al. (2012); Walsh et?al. (2012), and Wang et?al. (2012) examine how adaptive immune responses to acute and chronic lymphocyte choriomeningitis virus infection are regulated by type 1 interferon produced early during infection by different cell types upon activation by intracellular nucleic acid sensors.     

Synapses let loose for a change: inhibitory synapse pruning throughout experience-dependent cortical plasticity

In this issue of Neuron, Chen et?al. (2012) and van Versendaal et?al. (2012) used fluorescently tagged gephyrin to track inhibitory synapses in the mouse visual cortex in?vivo. Their studies show that visual experience-dependent plasticity is associated with clustered and location-specific pruning of inhibitory synapses.     

S1P(1) Bridges Mechanotransduction and Angiogenesis during Vascular Development

Mechanisms of stabilization of the vascular plexus and the role of mechanotransduction in this process are?not well understood. In this issue of Developmental Cell, Jung et?al. (2012) and Gaengel et?al. (2012) describe the ligand-sensitive and mechanosensitive functions of an important vascular G protein-coupled receptor, S1P(1).     

Cullin RING Ligases: Glommed by Glomulin

Cullin ring ligases (CRLs) constitute the largest group of RING finger ubiquitin ligases. Two recent studies in?Molecular Cell describe glomulin as a CRL1 inhibitor that blocks interactions with its ubiquitin-conjugating enzyme (E2) (Duda et?al., 2012; Tron et?al., 2012). These findings and their significance are discussed.     

Axon trapping: constructing the visual system one layer at a time

Zhang et?al. (2012) and Rozas et?al. (2012) in this issue of Neuron find that cysteine string protein α, a protein involved in neurodegeneration, regulates vesicle endocytosis via interaction with dynamin 1, which may participate in regulating synaptic transmission and possibly in maintaining synapses.     

The mitochondrial pyruvate carrier: has it been unearthed at last?

The mitochondrial pyruvate carrier (MPC) is essential for several major pathways of carbohydrate, fat, and amino acid metabolism, yet its molecular identity has remained elusive. Two recent papers in Science (Herzig et?al., 2012; Bricker et?al., 2012) implicate three newly identified inner mitochondrial membrane proteins as MPC components.     

Hijacking leucyl-tRNA synthetase for amino acid-dependent regulation of TORC1

TORC1 activity in all eukaryotes is dependent on amino acid availability. However, the mechanism through which TORC1 senses amino acids is still a mystery. In the current issues of Molecular Cell and Cell, Bonfils et?al. (2012) and Han et?al. (2012) implicate leucyl-tRNA synthetase in this evolving story.     

TXNIP Switches Tracks toward a Terminal UPR

During the progression of diabetes, crosstalk between ER stress and inflammation controls islet cell fate. In this issue, Lerner et?al. (2012) and Oslowski et?al. (2012) discover that thioredoxin-interacting protein (TXNIP) is a regulatory switch connecting the terminal unfolded protein response (UPR) and NLRP3 inflammasome to mediate β cell death.     

Unwinding to recombine

The MCM proteins are best known for their role in DNA replication, MCM2-7 forming the replicative helicase. Now, two reports in this issue of Molecular Cell, Nishimura et?al. (2012) and Lutzmann et?al. (2012) show the less well understood MCM8 and MCM9 to be crucial for effective homologous recombination.     

Transmitter time: synaptic plasticity and metabolic memory in the hypothalamus

Hunger elicits feeding behavior by activating Agouti-related peptide (AgRP) neurons. Two recent studies show how fasting, or the hunger hormone ghrelin, promote excitatory glutamate release onto AgRP neurons (Yang et?al., 2011) and increase postsynaptic glutamate receptor-mediated drive (Liu et?al., 2012).     

Autophagy works out

Autophagy is generally considered to be a cytoprotective response to stress, whether in the form of nutrient deprivation or the presence of dysfunctional organelles. He et?al. now show in Nature that exercise-induced autophagy is needed for some of the beneficial effects of exercise on metabolism (He et?al., 2012).     

UBAP1: a new ESCRT member joins the cl_Ub

The ESCRTs play multiple roles within the cell, including degradation of ubiquitinated membrane proteins by sorting them into multivesicular bodies (MVBs). Two recent studies provide structural and functional insights into how the newly identified ESCRT-I component UBAP1 dedicates ESCRT-I function for sorting ubiquitinated proteins at the MVB (Agromayor et?al., 2012 [this issue of Structure]; Stefani et?al., 2011).     

Brucella "hitches a ride" with autophagy

Autophagy involves lysosomal-mediated degradation of cellular components and contributes to host immunity. Some pathogens avoid autophagy-mediated killing, while others exploit it to acquire host cell nutrients. Starr et?al. reveal that the intracellular bacterial pathogen Brucella abortus can "hitch a ride" with autophagy, subverting autophagy machinery to spread from cell to cell (Starr et?al., 2012).     

Calcium and repression in malaria sex: knowing when the time is right

Plasmodium falciparum PfEMP1 is a malaria virulence protein whose expression is epigenetically regulated. The parasite's ability to express exclusively only one of the sixty var genes that encode PfEMP1 is essential for disease pathogenesis. Two recent papers identify key molecular players in determining whether a var gene is active or silenced (Volz et?al., 2012; Zhang et?al., 2011).     

The mycobiome: influencing IBD severity

The etiology and maintenance of inflammatory bowel disease (IBD) is the subject of much speculation. Iliev?et?al. (2012) impose a change in our views of the gut microbiome and catapult the fungal "mycobiome" center-stage in the exploration of IBD.     

Human structural plasticity at record speed

How rapidly does learning shape our brains? A new study in this issue of Neuron by Sagi et?al. (2012) that uses diffusion magnetic resonance imaging in both humans and rats suggests that just 2?hr of spatial learning is sufficient to change brain structure.