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Human Caco2 intestinal epithelial cells expressing a mutant version of the motor protein Myo5B recapitulate the phenotype of patients with microvillus inclusion disease, such as the subapical accumulation of secretory vesicles and the redistribution of microvilli from the apical brush border to intracellular inclusions. Vogel et al. reveal that, together with a group of membrane trafficking proteins including the SNARE protein syntaxin3, Myo5B mediates the selective delivery of specific cargoes to the apical plasma membrane.
Image © 2015 Vogel et al.
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In This Issue
In Focus
Solidifying the view of RNP dynamics
An RNAi screen provides new insights into the regulation of RNP granules and mRNA repression.
People & Ideas
Anne Brunet: Gracefully studying how we age
Brunet studies longevity, aging, and epigenetics in established and novel model systems.
From the Archive
SUMO enters the ring
In 1996, Matunis et al. were one of several groups to identify a novel, ubiquitin-like protein modification.
Review
Report
Discs of mammalian rod photoreceptors form through the membrane evagination mechanism
Ultrastructural analysis of membrane organization in mouse rod cells demonstrates that new photoreceptor discs are contiguous evaginations of the outer segment plasma membrane, thereby resolving the debate of whether discs are formed through membrane evagination or intracellular vesicular fusion.
Article
TRIP13PCH-2 promotes Mad2 localization to unattached kinetochores in the spindle checkpoint response
The ability of the conserved ATPase TRIP13PCH-2 to disassemble a Mad2-containing complex is critical to promote the spindle checkpoint response by contributing to the robust localization of Mad2 to unattached kinetochores.
Bub3–BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes
BubR1 depends on its association with Bub3 to localize on DNA breaks during mitosis, where it sequesters Cdc20Fizzy and induces the inhibition of the APC/C locally, promoting the faithful segregation of broken chromatids.
Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes
Reduction of lamin A/C, which is evolutionarily required for the modulation of Polycomb group (PcG) protein–dependent transcriptional repression by sustaining PcG protein nuclear architecture, leads to PcG protein diffusion and to muscle differentiation.
Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells
Cdc42 control of actin dynamics keeps DCs in an immature state, and loss of Cdc42 activity facilitates secretion and rapid up-regulation of intracellular molecules to the cell surface, which shows that Cdc42 contributes to DC immunogenicity by regulating the DC actin cytoskeleton.
Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels
TRIM3 regulates synaptic γ-actin levels. TRIM3-deficient mice consequently have higher hippocampal spine densities, increased long-term potentiation, and enhanced contextual fear memory consolidation, indicating that temporal control of ACTG1 levels by TRIM3 is required to constrain hippocampal plasticity within physiological boundaries.
Cargo-selective apical exocytosis in epithelial cells is conducted by Myo5B, Slp4a, Vamp7, and Syntaxin 3
The motor protein Myo5B and t-SNARE Stx3 drive cargo-selective apical exocytosis in polarized epithelial cells in a pathway dependent on v-SNARE–like Slp4a, v-SNARE Vamp7, Sec1/Munc18-like protein Munc18-2, and the Rab11/8 cascade.
Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling
COMMD protein family member COMMD9 regulates the endosome to plasma membrane trafficking of Notch through a unique COMMD–CCDC22–CCDC93 (CCC) complex.
AMIGO2, a novel membrane anchor of PDK1, controls cell survival and angiogenesis via Akt activation
AMIGO2 is a novel scaffold protein that regulates PDK1 membrane localization and Akt activation in endothelial cells, and inhibition of the interaction between PDK1–AMIGO2 results in impaired neovascularization, pathological angiogenesis, and tumor angiogenesis.
Membrane-anchored ubiquitin ligase complex is required for the turnover of lysosomal membrane proteins
VAcUL-1 and Dsc, two different E3 ubiquitin ligase complexes coexist on the vacuole membrane to regulate different subsets of membrane proteins via the vReD pathway in response to different environmental cues.
The DYRK-family kinase Pom1 phosphorylates the F-BAR protein Cdc15 to prevent division at cell poles
In rod-shaped fission yeast cells, the DYRK-family kinase Pom1, which localizes at cell poles, inhibits the formation of the contractile actomyosin ring at these regions by phosphorylating the key ring component, F-BAR protein Cdc15, allowing the ring to slide toward the middle of the cell.
GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells
Crispr/Cas9-mediated mutation of the transcription factor GRHL2 or either of its predicted downstream targets ZNF750 and SMAGP in primary human bronchial epithelial basal cells leads to defects in ciliogenesis and/or barrier function.
Protrusive waves guide 3D cell migration along nanofibers
Reductionist approaches based on 3D fibers reveal that single-cell migration along fibers is driven by lateral actin-based waves for various cell types.
Tools
Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development
Modifiers of aberrant solid RNP granules suggest new insights into pathways that control dynamics of large-scale RNP bodies and mRNAs during C. elegans oogenesis.
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