People & Ideas
Yogesh Kulathu studies signaling mechanisms with a focus on ubiquitin and other post-translational modifications such as UFMylation.
Vladimir Sirotkin previews work from Wirshing and colleagues, which examines how competition between formins and capping proteins for the barbed ends of actin filaments modulates actin networks.
Patrick T. Caswell discusses work from Bryant and colleagues which shows how ARF3 impacts metastasis in prostate cancer by regulating a switch between modes of collective invasion.
Melissa Parker and Katrin Karbstein review our current understanding of the quality control mechanisms governing ribosome assembly.
Cieslinski and Wu et al. employ super-resolution microscopy to obtain a comprehensive model of the kinetochore structure in budding yeast. By measuring precise positions and stoichiometries, they could resolve the arrangement of the major kinetochore subunits when under attachment tension during metaphase.
Unraveling the kinetochore nanostructure in Schizosaccharomyces pombe using multi-color SMLM imaging
Virant et al. build an in situ model of the Schizosaccharomyces pombe kinetochore by determining inter-protein distances and copy numbers. Next to confirming its conserved nature known from in vitro data, they point out S. pombe specifics, e.g., within DASHc and the inner kinetochore structure.
Du et al. show that Tex2, a potential lipid transporter on the tubular endoplasmic reticulum, is recruited to late endosomes/lysosomes by endosome-resident phosphatidylinositol 4-phosphatases TMEM55 to regulate the lipid compositions, trafficking, and the functions of lysosomes.
Xie et al. demonstrate how an acidic patch in the β′-COP subunit of the yeast COPI coat serves as a critical recognition site for binding conserved basic residues in the ArfGAP, Glo3. Loss of this COPI/Glo3 molecular link affects recycling of specific transmembrane proteins trafficked through endosomes and the TGN.
The outer mitochondrial membrane protein TMEM11 demarcates spatially restricted BNIP3/BNIP3L-mediated mitophagy
Gok et al. describe a role for the mitochondrial outer membrane protein TMEM11 in the spatial regulation of receptor-mediated mitophagy. Upon mitophagy induction, TMEM11 co-enriches with BNIP3 and BNIP3L at mitophagy sites. However, in the absence of TMEM11, mitophagy sites are dysregulated and drastically increase in number along the mitochondrial membrane.
Jaffray et al. demonstrate that the arsenic-induced, SUMO and ubiquitin-mediated degradation of the PML protein and its oncogenic variant PML-RARA is dependent upon the VCP/p97 segregase protein.
Human atlastins are sufficient to drive the fusion of liposomes with a physiological lipid composition
Atlastins regulate the structure and function of the endoplasmic reticulum (ER). In this study, using reconstituted proteoliposomes with a lipid composition mimicking that of the ER, Jang et al. show that all human atlastins are sufficient to drive membrane fusion.
Evolutionary tuning of barbed end competition allows simultaneous construction of architecturally distinct actin structures
Competition at barbed ends between capping proteins and formins leads to the assembly of architecturally distinct cellular actin structures and the differential sorting of actin-binding proteins to each structure.
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease whose molecular etiology remains mostly enigmatic. By discovering an antagonistic relationship between the tumor suppressors Prdm16 and Smad4 in PDAC, this study paves the way for innovative frameworks with potential therapeutic implications.
Zhu et al. identify a critical role for a heretofore undescribed interaction between a dual set of metalloproteins, Mmp9 and Mmp14, and the carbohydrate-binding protein galectin-3, whose binding interaction with the transmembrane receptor Lrp-1 shapes the transcriptional programs and signaling cascades directing osteoclast-mediated bone resorption.
Larsson et al. demonstrate that the large GTPase dynamin 2 does not mediate fission of caveolae from the plasma membrane as previously thought. Instead, dynamin 2 associates with a subset of caveolae and functions to restrain caveolae to the plasma membrane via a GTPase-independent mechanism.
Van den Berg et al. provide insight into the biochemical mechanisms of the assembly and maintenance of stable microtubule structures in the cilia by dissecting how the ciliopathy-linked protein CSPP1 stabilizes microtubules from the inside.
Safavian et al. show that septins and the associated RhoA GTP exchange factor ARHGEF18 regulate primary ciliogenesis by locally activating RhoA, leading to the activation of the exocyst complex and the subsequent recruitment of transition zone components.
Bebelman and Bovyn et al. demonstrate that apical bulkheads, connections between the apical membranes of opposing hepatocytes, are load-bearing mechanical elements that contribute to the ability of bile canaliculi to withstand elevated luminal pressure.
Sandilands et al. show that ARF3 acts as a rheostat for the modality of invasion via association with, and control of, N-cadherin turnover. This ARF3/N-cadherin interaction regulates metastasis in vivo and can identify prostate cancer patients with metastatic, poor-outcome disease.
Kozar-Gillan and colleagues reveal a novel molecular pathway in node of Ranvier formation by demonstrating that LGI3/2–ADAM23 interactions cluster and stabilize Shaker-type voltage-gated potassium channels (Kv1) in myelinated axons. These myelin concealed Kv1 channels contribute to basic axonal properties to secure reliable high-frequency firing.
Ashour et al. present a mass spectrometry–based tool to assay DNA replication. The technique, termed mass-spectrometry–based analysis of nascent DNA (MS-BAND), permits quantitation of replication in human and bacterial cells, as well as mitochondria. MS-BAND can perform higher-throughput replication analysis, which may prove advantageous compared to established methods.
Quantifying organellar ultrastructure in cryo-electron tomography using a surface morphometrics pipeline
Barad and Medina et al. present a pipeline for quantifying the architecture of organellar membranes in cells visualized by cryo-electron tomography. They use this pipeline to detect changes in the membrane ultrastructure of fragmented and elongated mitochondria and identify statistically significant changes upon induction of ER stress.
Semi-automated 3D fluorescence speckle analyzer (3D-Speckler) for microscope calibration and nanoscale measurement
Loi et al. introduce 3D-Speckler, a powerful and high-throughput image analysis software with a user-friendly interface that offers semi-automated, multi-dimensional measurements and corrections of fluorescent particles including 2D/3D size, localization with nanometer accuracy, and intensity for routine microscope calibration and quantitative analyses of biological structures.