On the cover
A tomogram-derived scheme shows the interface between a Drosophila flight muscle myotube and a closely apposed myoblast as they fuse with one another. Dhanyasi et al. suggest that contact sites (green) within the apposed surface membranes (pink) give rise to small pores (red), which then expand, leading to cytoplasmic continuity and complete fusion.
Image © 2015 Dhanyasi et al.
See page 191.
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In This Issue
Thy-1: Shade and sun for integrin signaling
The GPI-anchored protein Thy-1 can both promote and inhibit integrin activity.
People & Ideas
Lin He: “Junk” DNA isn’t
He studies how the noncoding genome shapes development and cancer.
From the Archive
Lamellipodial actin branches out
In the late 1990s, Tatyana Svitkina and colleagues described how actin is organized at the leading edge of migrating cells.
RanGTP aids anaphase entry through Ubr5-mediated protein turnover
Cells sense the overall chromosome congression state in metaphase to promote anaphase entry using RanGTP, which induces the reduction of two spindle assembly checkpoint proteins, BuGZ and Bub3, via the E3 ligase Ubr5.
Polarity establishment requires localized activation of Cdc42
Positive feedback by localized activation of Cdc42 drives polarity establishment in the budding yeast Saccharomyces cerevisiae.
RAL-1 controls multivesicular body biogenesis and exosome secretion
In Caenorhabditis elegans, the RAL-1 GTPase regulates multivesicular body formation and fusion with the plasma membrane, thereby promoting exosome secretion; in mammals, RalA and RalB are required for the secretion of exosome-like vesicles.
Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells
Blocking β-catenin/TCF1–mediated transcriptional activation with a specific small molecule or by TCF1 knockdown delays the mouse embryonic stem cell differentiation program and enhances pluripotency.
Caveolae protect endothelial cells from membrane rupture during increased cardiac output
This study provides direct in vivo evidence that endothelial cell caveolae disassemble and hence flatten out under increased mechanical stress and that the presence of caveolae protects endothelial cell plasma membranes from damage.
Intranuclear binding in space and time of exon junction complex and NXF1 to premRNPs/mRNPs in vivo
The exon junction core complex associates with Balbiani ring (BR) premRNPs during transcription and in relation to splicing, whereas the export factor NXF1 is recruited in the interchromatin, and BR mRNPs become export competent only after passage through the interchromatin.
SAM68 is a physiological regulator of SMN2 splicing in spinal muscular atrophy
Knockout of the splicing factor SAM68 promotes SMN2 splicing, improving neuromuscular defects and viability in SMA mice.
Ribosome binding induces repositioning of the signal recognition particle receptor on the translocon
The cotranslational transfer of nascent membrane proteins to the SecYEG translocon is facilitated by a reorientation of the SecY-bound signal recognition particle (SRP) receptor, FtsY, which accompanies the formation of a quaternary targeting complex consisting of SecYEG, FtsY, SRP, and the ribosome.
mTORC2 promotes cell survival through c-Myc–dependent up-regulation of E2F1
Inactivation of mTORC2 reduces PP2A activity toward c-Myc serine 62 (S62), leading to enhancement of c-Myc phosphorylation and expression and increased transcription of pri-miR-9-2/miR-9-3p, which in turn suppresses E2F1 and enhances apoptosis.
APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments
APPL1 vesicles represent a distinct population of Rab5-positive early endosomes that undergoes fusion and fission and sorts and exchanges cargo with EEA1 endosomes, suggesting a new organization of the endocytic pathway.
Prion aggregate structure in yeast cells is determined by the Hsp104-Hsp110 disaggregase machinery
3D structural analysis of a yeast [PSI+] prion model by correlative fluorescence and electron tomography reveals that prion aggregate structure depends on the levels of Hsp70 chaperones, the protein remodeling ATPase Hsp104, and the Hsp70 nucleotide exchange factor/disaggregase Sse1 (yeast Hsp110).
Growth factor signaling to mTORC1 by amino acid–laden macropinosomes
Growth factor–stimulated macropinocytosis rapidly delivers extracellular amino acids into endolysosomes for activation of mTORC1, indicating a vesicular pathway of signaling for cell growth.
Conformational coupling of integrin and Thy-1 regulates Fyn priming and fibroblast mechanotransduction
Lateral associations between inactive αv integrin and Thy-1 glycoprotein control integrin avidity to extracellular matrix ligand, the localization and kinetics of downstream signal activity, and mechanosensitive remodeling of the cytoskeleton.
Surface apposition and multiple cell contacts promote myoblast fusion in Drosophila flight muscles
Transmission EM methods reveal that cell–cell fusion of individual myoblasts with growing Drosophila flight muscles is a stepwise process in which the cell adhesion and branched actin machineries mediate tight apposition and formation of multiple contacts and pores between the surfaces of the fusing cells.