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    On the cover
    Fixed bovine pulmonary artery endothelial (BPAE) cells imaged with 3D-structured illumination super-resolution microscopy (3D-SIM; GE OMX Blaze). Cellular components are shown: actin (blue), mitochondria (yellow), and DNA (white). Image © 2016 Lambert and Waters
    See page 53.

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ISSN 0021-9525
EISSN 1540-8140
In this Issue

In Focus

People & Ideas

Ewald takes a multidisciplinary collaborative approach to study epithelial morphogenesis

In Memoriam

Spotlight

Frazier and Jackson discuss work by Kadlecova et al. in which they monitored the temporal regulation of clathrin-mediated endocytosis in real time.

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.

Pierobon and Lennon-Duménil highlight recent findings on how the mechanical properties of membranes affect uptake of surface-tethered antigen by B lymphocytes.

Viewpoint

Sidoli, Kulej, and Garcia discuss their view of what mass spectrometry brings to cell biology today and in the future.

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.

Celeste M. Nelson shares her view of the big picture of current and future progress in technologies for force measurement.

Perspective

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.

Review

Monachino et al. review recent developments in single-molecule biophysical approaches and the cell biological advances they allow.

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.

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.

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.

Report

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.

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.

Article

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.

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.

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.

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.

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.

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.

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.

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 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.

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 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.

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