ON THE COVER
Artistic representation of zebrafish retina (white), highlighting individually taken microscopy images of four major neurogenic lineages. One retinal ganglion cell with two photoreceptors (red), an amacrine cell with one bipolar cell (yellow), an amacrine cell with two photoreceptors (green), and two bipolar cells (blue). Image © Wang et al., 2020 https://doi.org/10.1083/jcb.202003026
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Programming pluripotent stem cells: Can't teach an old cell new DNA replication tricks
Mouery, Mei, and Cook discuss new work from the Gerhardt laboratory showing incomplete DNA replication reprogramming in induced pluripotent stem cell lines that have lower differentiation potential.
Long noncoding RNA amplified in lung cancer rewires cancer pathways
Martínez-Terroba and Dimitrova preview work from Athie et al., which demonstrates that the lncRNA ALAL-1 promotes lung cancer cell proliferation and immune evasion.
Mitophagy is induced by short ubiquitin chains on mitochondria
Fumiyo Ikeda discusses recent work from Yamano et al. discovering a role for OPTN and ATG9A in the induction of mitophagy.
Role of the early secretory pathway in SARS-CoV-2 infection
Sicari et al. discuss the early secretory pathway in the SARS-CoV-2 infection cycle and provide a perspective on potential therapeutic implications.
Evolving models for assembling and shaping clathrin-coated pits
Integrating recent findings, Chen and Schmid present a more dynamic, flexible, and nonlinear model for clathrin-coated vesicle formation.
Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator
Gómez Acuña et al. show that human Argonaute-1 (AGO1) binds genome wide to estrogen receptor α sites at chromatin and acts as a coactivator of estrogen-mediated transcriptional activation. This new role for AGO1 does not depend on binding to small RNAs.
In situ cryo-electron tomography reveals filamentous actin within the microtubule lumen
Paul et al. use cryo-ET to show that microtubules can contain actin filaments in their lumen. Two types of F-actin structure are distinguished, Class I and Class II, with slightly different helical symmetries and outer microtubule diameters. They call these filaments microtubule lumenal actin (ML-actin).
The function of GORASPs in Golgi apparatus organization in vivo
Grond et al. show that GRASPs or GORASPs do not have a role in stacking of Golgi cisternae in vivo but instead are required for linking cisternal rims to likely control flux of transport through the Golgi apparatus.
Cancer cells educate natural killer cells to a metastasis-promoting cell state
Chan et al. show that natural killer (NK) cells can be reprogrammed by breast cancer cells to promote metastasis. Reprogramming can be blocked by targeting NK cell inhibitory receptors TIGIT or KLRG1 or inhibiting DNA methyltransferases, which suggests new approaches to prevent or treat metastasis.
G1/S transcription factors assemble in increasing numbers of discrete clusters through G1 phase
Super-resolution imaging shows that G1/S transcription factors in budding yeast are spatially organized in small clusters that increase in number, not molecular content, as the transcription factor copy number increases with cell growth in G1. This spatial and temporal organization of the G1/S regulon might help coordinate the Start transition.
Pluripotent stem cells with low differentiation potential contain incompletely reprogrammed DNA replication
Differentiation potential varies among reprogrammed pluripotent stem cells (PSCs), but the factors contributing to this variability are not understood. Paniza et al. show that reprogramming of DNA replication is incomplete and genomic instability is increased in PSCs with low differentiation potential.
Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion
The pro-oncogenic lncRNA ALAL-1 is frequently amplified in lung adenocarcinomas. ALAL-1 is induced by TNFα and, by interacting with SART3, promotes the nuclearization of USP4, affecting TNFα, p53, NF-κB, and TGF-β1 pathways. ALAL-1 expression in lung squamous tumors correlates with lower levels of immune infiltration.
EGF receptor–mediated FUS phosphorylation promotes its nuclear translocation and fibrotic signaling
Chiusa et al. show that the RNA-DNA binding protein FUS plays a profibrotic role by binding to the collagen IV gene promoter and commencing its transcription. Reducing nuclear FUS inhibits collagen IV transcription, suggesting that targeting FUS offers a new antifibrotic therapy.
The +TIP Navigator-1 is an actin–microtubule crosslinker that regulates axonal growth cone motility
Sanchez-Huertas et al. demonstrate that the +TIP Navigator-1 (NAV1) couples F-actin and microtubules in the growth cone of cortical axons. This property enables NAV1 to promote microtubule persistence in the growth cone periphery and controls growth cone dynamics and steering.
Branched actin networks are assembled on microtubules by adenomatous polyposis coli for targeted membrane protrusion
Efimova et al. show that adenomatous polyposis coli (APC) at microtubule tips triggers assembly of a branched actin network when the microtubule hits the plasma membrane in neuronal growth cones. These findings uncover a new mechanism of microtubule-dependent cell navigation.
The kinesin-like protein Pavarotti functions noncanonically to regulate actin dynamics
The centralspindlin complex, comprising Tumbleweed RhoGAP and kinesin-like Pavarotti proteins, associates with microtubules during cytokinesis. Nakamura et al. show that Pavarotti has centralspindlin complex–independent functions, binds directly to actin, and regulates actin dynamics during cell wound repair and oogenesis.
CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion
Farrugia et al. identify Cdc42EP5 as a regulator of actomyosin activity. Cdc42EP5 potentiates SEPT9-mediated F-actin bundling, which is required for the stabilization of highly contractile actomyosin structures. In melanoma, the Cdc42EP5–SEPT9 axis is required for amoeboid migration, invasion, and metastasis.
Critical role of mitochondrial ubiquitination and the OPTN–ATG9A axis in mitophagy
Damaged mitochondria are selectively eliminated by Parkin/PINK1-mediated autophagy. Yamano et al. show that in addition to binding ATG8 proteins, one of the critical autophagy adaptors, OPTN, possesses an ATG9A binding site that contributes to de novo synthesis of autophagosomal membranes.
PTEN dephosphorylates Abi1 to promote epithelial morphogenesis
The tumor suppressor PTEN is essential for epithelial morphogenesis. Qi et al. identify Abi1, a core adaptor protein in the WAVE regulatory complex, as a new PTEN substrate. PTEN dephosphorylates Abi1 and causes Abi1 degradation through calpains and thus down-regulates the WAVE regulatory complex to induce epithelial differentiation and polarization.
Mutual antagonism between Hippo signaling and cyclin E drives intracellular pattern formation
Jiang and colleagues investigate how locations of sites of organelle assembly are determined during cell division in the ciliate Tetrahymena thermophila. They find that correct placement of new organelles involves antagonistic influences of a cyclin E and a Hippo/Mst kinase.
Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis
Chen et al. define the role of the N-terminal domain (TD) of clathrin heavy chain in early and late stages of clathrin-mediated endocytosis (CME) and design a membrane-permeant peptide, Wbox2, that acutely and potently inhibits CME.
Alternative splicing of clathrin heavy chain contributes to the switch from coated pits to plaques
A single alternatively spliced exon in the CLTC gene contributes to clathrin coat organization. This event participates in the plasticity from clathrin-coated pits to plaques, structures that are essential for muscle fiber function and maintenance.
Intersection of TKS5 and FGD1/CDC42 signaling cascades directs the formation of invadopodia
Cancer cell dissemination is facilitated by actin-rich plasma membrane protrusions called invadopodia, which focally degrade matrix tissues. Zagryazhskaya-Masson et al. show that invadopodia formation and function depend on the interaction between the scaffolding protein, TKS5, and the CDC42 guanine exchange factor, FGD1.
mRNA localization mediates maturation of cytoplasmic cilia in Drosophila spermatogenesis
Cytoplasmic cilia, which are found in human and Drosophila sperm, are unique in that the axoneme is exposed to the cytoplasm. Fingerhut and Yamashita show that localization of a novel RNP granule containing axonemal dynein mRNAs facilitates incorporation of these axonemal proteins, promoting cytoplasmic cilia formation.
Deorphanizing FAM19A proteins as pan-neurexin ligands with an unusual biosynthetic binding mechanism
Synaptic properties are controlled by trans-synaptic adhesion complexes. Neurexins are central components of these complexes, but how neurexins are regulated remains largely unknown. Khalaj et al. identify FAM19A1-A4 as neuronal activity–regulated proteins that form covalent complexes with neurexins and regulate their post-translational modifications, thus shaping neurexin–ligand interactions and synapse properties.
Different lineage contexts direct common pro-neural factors to specify distinct retinal cell subtypes
Combining in vivo lineage tracing and single-cell RNA- and ATAC-seq, Wang et al. identified a repertoire of stereotyped neurogenic lineages in the developing zebrafish retina, revealing the lineage logic of neuron type/subtype specification and respecification in a vertebrate CNS structure.
Tyramide signal amplification mass spectrometry (TSA-MS) ratio identifies nuclear speckle proteins
Dopie et al. apply TSA-MS ratio, an approach that compares the abundance of proteins in nuclear speckles with centromeres to reduce nonspecific background, and show that MFAP1 levels modulate nuclear speckle size and MFAP1 is recruited early to reforming nuclear speckles after mitosis.
Correction: The function of GORASPs in Golgi apparatus organization in vivo