January 2017 | Volume 216, No. 1
People & Ideas
- ARF1 at the crossroads of podosome construction and function
Elisabeth Genot highlights a paper by Rafiq et al. that reveals a role for the small GTPase ARF1 in the regulation of podosome formation and function.
- To use or not to use the force: How B lymphocytes extract surface-tethered antigens
Pierobon and Lennon-Duménil highlight recent findings on how the mechanical properties of membranes affect uptake of surface-tethered antigen by B lymphocytes.
- Why proteomics is not the new genomics and the future of mass spectrometry in cell biology
Sidoli, Kulej, and Garcia discuss their view of what mass spectrometry brings to cell biology today and in the future.
- Interrogating cellular perception and decision making with optogenetic tools
In this Viewpoint article, Wendell A. Lim and colleagues examine the ways by which optogenetic tools and techniques are being used to query cellular signaling and function.
- Organoids: A historical perspective of thinking in three dimensions
In this perspective, Simian and Bissell discuss the evolution of the 3D culture and organoid research field up to now as well as its future directions.
- Navigating challenges in the application of superresolution microscopy
In this review, Lambert and Waters focus on the current practical limitations of superresolution microscopy (SRM) and provide information and resources to help biologists navigate through common pitfalls when designing an SRM experiment.
- Machine learning and computer vision approaches for phenotypic profiling
Grys et al. review computer vision and machine-learning methods that have been applied to phenotypic profiling of image-based data. Descriptions are provided for segmentation, feature extraction, selection, and dimensionality reduction, as well as clustering, outlier detection, and classification of data.
- Mammalian synthetic biology for studying the cell
Novel approaches in mammalian synthetic biology are advancing the study of cellular processes, regulatory networks, and multicellular interactions. Mathur et al. describe how the design of sophisticated genetic components supported by quantitative standards and computational tools will continue to expand the impact of synthetic biology on cell biology research.
- Two distinct membrane potential–dependent steps drive mitochondrial matrix protein translocation
Schendzielorz et al. report that mitochondrial precursors display different dependencies on the membrane potential (Δψ) for translocation. Two distinct Δψ-dependent steps promote precursor translocation, the first driving presequence translocation and the second acting on the mature portion of the polypeptide chain.
- Activating the nuclear piston mechanism of 3D migration in tumor cells
Petrie et al. show that inhibiting matrix metalloproteinases during 3D tumor cell migration activates the fibroblast-associated nuclear piston mechanism of intracellular pressure generation to slow tumor cell movement.
- Constitutive centromere-associated network controls centromere drift in vertebrate cells
Hori et al. show that centromere position can be drifted during cell proliferation in chicken DT40 cells. However, the centromere drift is suppressed in short-term cultures, and a complete constitutive centromere-associated network organization contributes to the suppression of the centromere drift.
- 4E-BP is a target of the GCN2–ATF4 pathway during Drosophila development and aging
Kang et al. show that the GCN2–ATF4 pathway induces 4E-BP transcription in response to amino acid deprivation and also during the development of certain Drosophila tissues. 4E-BP has selective effects on translation; therefore, this pathway helps to shift the mRNA expression profiles of cells.
- An inducible ER–Golgi tether facilitates ceramide transport to alleviate lipotoxicity
Liu et al. show that ER–Golgi tethering increases during ER stress in yeast. The protein Nvj2p is required for this tethering, which promotes nonvesicular ceramide transport from the ER to the Golgi to alleviate ceramide toxicity.
- Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
Chung et al. show that the myomitokine GDF15 can act to modulate oxidative and lipolytic function in a non–cell-autonomous manner, thereby regulating systemic energy homeostasis in skeletal muscle-specific Crif1-deficient mice. This pathway may be a potential therapeutic target for preventing the onset of obesity and insulin resistance.
- Regulation of clathrin-mediated endocytosis by hierarchical allosteric activation of AP2
The adaptor AP2 is required for initiation of clathrin-mediated endocytosis. Kadlecova et al. delineate the functional hierarchy of AP2 interactions with phosphatidylinositol lipids and cargo and their relationship to distinct steps in clathrin-coated pit nucleation and maturation in living cells.
- Podosome assembly is controlled by the GTPase ARF1 and its nucleotide exchange factor ARNO
Rafiq et al. demonstrate that the small G protein ARF1 and its activator, cytohesin 2 (ARNO), are required for podosome formation in macrophage-like cells and fibroblasts. Inhibition of ARNO-ARF1 signaling results in increased RhoA activity and disassembly of podosomes in a myosin-IIA–dependent fashion. In fibroblasts that normally do not form podosomes, constitutively active ARF1 induces actin-rich puncta associated with sites of matrix degradation, putative precursors of podosomes.
- A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib
Semaphorins are ligands for their receptors, plexins. In this study, Sun et al. show that a transmembrane semaphorin, Sema4A, transduces signals in a reverse manner to control migration of cancer and dendritic cells via the cell polarity protein Scrib.
- B cell antigen extraction is regulated by physical properties of antigen-presenting cells
To mount antibody responses, B cells need to extract antigens from antigen-presenting cells (APCs). Using new DNA nanosensors, Spillane and Tolar show that B cell antigen extraction occurs via mechanical forces and is regulated by physical properties of the APCs.
- Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release
Fife is a Piccolo-RIM–related protein that regulates neurotransmission and motor behavior through an unknown mechanism. Here, Bruckner et al. show that Fife organizes synaptic vesicle docking and coupling to calcium channels to establish and modulate synaptic strength.
- INPP5E regulates phosphoinositide-dependent cilia transition zone function
Dyson et al. demonstrate that the inositol polyphosphate 5-phosphatase INPP5E is essential for Hedgehog-dependent embryonic development. By regulating PI(4,5)P2 and PI(3,4,5)P3 signals at cilia, INPP5E contributes to cilia transition zone function and thereby Smoothened accumulation at cilia.
- The palmitoyltransferase Approximated promotes growth via the Hippo pathway by palmitoylation of Fat
The palmitoyl transferase Approximated regulates signaling by the protocadherin Fat to control tissue growth upstream of the Hippo pathway in Drosophila. Matakatsu et al. show that palmitoylation of the intracellular domain of Fat by Approximated negatively regulates Fat and its ability to restrict growth.