People & Ideas
JCB checks in with newly independent cell biologists and learns about their experience running a lab during the COVID-19 pandemic.
Visintin and Marston discuss the life and achievements of Angelika Amon, who passed away on October 29, 2020.
Bogan highlights work from Müller et al. that examines the effects of glucose stimulation on microtubule organization and insulin secretory granule exocytosis in β cells.
Hadders and Lens preview work from the Zachos laboratory describing a new pathway activating the abscission checkpoint during cytokinesis.
Latour and McGuigan highlight work from the Derivery laboratory that describes a new method for micropatterning proteins while maintaining their activity using fibrinogen anchors.
Behmoaras and Gil describe shared cellular features between senescent cells and macrophages and outline the interaction between the two cell types during homeostasis and disease.
The synaptonemal complex promotes faithful exchanges between homologous chromosomes during meiosis. Barbosa et al show that SCF-FBxo42 is important for assembly and maintenance of the synaptonemal complex by restricting the phosphatase PP2A-B56 level.
Polo-like kinase 1 independently controls microtubule-nucleating capacity and size of the centrosome
Centrosomes increase in microtubule nucleating capacity during mitotic entry to catalyze spindle assembly. Ohta et al. show that Polo-like kinase 1 enables this increase by independently controlling the physical expansion of centrosomes and the generation of centrosomal microtubule-nucleating sites.
Müller et al. provide the first full 3D reconstructions of microtubule networks in a mammalian cell, the islet β cell. Microtubules are mostly disconnected from centrioles and endomembranes, while associated with cortical insulin granules, highlighting their importance for regulated secretion.
Ma et al. describe a closed feedback loop between DSBs and microtubules during c-NHEJ. DSBs result in increased microtubule dynamics through interphase centrosome maturation in G1 cells, which requires DNA-PK-AKT and 53BP1. Increased microtubule dynamics facilitates c-NHEJ in G1 cells through elevating DSB mobility.
How cells delay completion of cytokinesis (abscission) in the presence of chromatin bridges is unclear. Petsalaki and Zachos describe an ATM–Chk2–INCENP signaling pathway that activates the abscission checkpoint to prevent chromatin breakage in cytokinesis.
Sato et al. demonstrate that MYC expression renders MCF10A cells sensitive to down-regulation of UVSSA, as it alleviates stress during MYC-dependent transcription. UVSSA is a promising novel target for attacking MYC-addicted cancer cells.
By systematic depletion of PCM proteins and centrioles in human cell lines, we reveal the cooperative role of the centriole and PCM scaffold proteins, pericentrin and CDK5RAP2, in the recruitment of CEP192 to spindle poles to promote bipolar spindle formation.
The intracellular position of lysosomes is critical for cell metabolism and signaling. Kesisova et al. discovered a membrane-associated septin GTPase scaffold of dynein–dynactin that promotes retrograde traffic and perinuclear lysosome clustering at steady state and in response to oxidative stress.
Rag GTPases and phosphatidylinositol 3-phosphate mediate recruitment of the AP-5/SPG11/SPG15 complex
The AP-5/SPG11/SPG15 complex is recruited onto late endosomes/lysosomes and contributes to lysosomal homeostasis and autophagic lysosome reformation. Hirst et al. show that recruitment is by coincidence detection, requiring both phosphatidylinositol 3-phosphate and Rag GTPases, thus uncovering a link between AP-5/SPG11/SPG15 and the mTORC1 pathway.
Lonic et al. show that phosphorylation of Y374-PKCδ by FER arrests the maturation of early to late endosomes by inhibiting the release of RAB5 from nascent late endosomes. This promotes EGFR recycling and sustained signaling in triple-negative breast cancer.
Kulasekaran et al. discover a novel GTPase cascade in which Arf5 activates Rab35. Disruption of this pathway increases EGF receptor activation, leading to upregulation of the transcription factor SPOCD1 with enhanced tumor growth and invasion in glioblastoma.
The small noncoding vault RNA is a component of the vault complex, a ribonucleoprotein complex found in most eukaryotes. Wakatsuki et al. show that vault RNA functions as a riboregulator of synaptogenesis by modulating the MAPK signaling pathway in neurons.
Liu et al. identify PpV, the Drosophila orthologue of catalytic subunit of PP6, as a direct target of Hedgehog signaling. PpV functions independent of its phosphatase activity to fine-tune Hedgehog signaling activities, thus forming a regulatory circuit to maintain homeostatic Hedgehog signaling.
Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes
Vellino et al. investigated the fine tuning between adhesive and extracellular matrix degradative functions of invadosomes. They characterized the importance of the calcium channel TRPV4 in this coupling through its unique ability to sense ROS and regulate the activities of β1-integrins and a new Ask1–MYO1C functional complex.
Zhang et al. identify CEP55 as a novel regulator of cilia disassembly. Their findings establish a cilia disassembly role for CEP55 in vivo and in vitro, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.
Kanfer et al. develop a pooled CRISPRi screening method to identify genes regulating intracellular protein localization, organelle morphology or other subcellular phenotypes. The method uses machine learning to identify genetically altered cells, a photoactivated fluorescent protein to label them, and FACS plus deep sequencing to identify the affected gene.
Yan et al. demonstrate high-throughput screening of pooled CRISPR libraries for phenotypes detectable by microscopy. Their approach uses photoactivation of cells displaying the phenotype of interest and FACS sorting of marked cells, followed by sequencing, and facilitates discovery of genes involved in cell biological processes.
Watson et al. describe a general method to improve protein printing on glass (also known as micropatterning) while maintaining protein activity. In particular, this enables subcellular micropatterning, whereby complex micropatterns are able to simultaneously control cell shape and imprint the distribution of transmembrane receptors within that cell.