People & Ideas
Hamidi and Ivaska preview work from the Korolchuk laboratory describing focal adhesions as hubs mediating growth factor signaling via mTORC1 and amino acid input into the cell.
Tight control of Cdc20 activity is required for proper cell division. Here, it is shown that the BubR1 checkpoint protein integrates both Cdc20 inhibition and activation. PP2A-B56 bound to BubR1 removes Cdc20 inhibitory phosphorylation, allowing for efficient mitotic exit.
Jones et al. determine the role of matrix stiffness in regulating chromatin accessibility in freshly isolated lung fibroblasts. They identify ZNF416 as a key transcriptional regulator controlling fibroblast activation by the mechanical environment with relevance to wound healing and fibrosis.
Calcium entry into the injured cell activates their repair, but how cells cope with this excess calcium is not fully understood. Chandra et al. show that cells sequester this calcium in the ER, which is compromised in muscular dystrophy caused by the loss of an ER-resident calcium-activated chloride channel.
Immunosenescence, or immune aging, is a hallmark of aging. This study shows that inhibition of insulin/IGF-1 receptor reverses immunosenescence in the roundworm Caenorhabditis elegans through a feedback circuit comprising FOXO, HSF-1, and bZIP transcription factors and an insulin-like peptide, INS-7.
FUS-dependent liquid–liquid phase separation is a critical process in the early activation of the DNA damage response and in the recruitment of key proteins, which facilitates the proper assembly of double-strand break repair complexes.
Nabais et al. use an egg explant system overexpressing Plk4 to study the spatiotemporal and biochemical regulation of de novo centriole assembly. They show that the onset and kinetics of biogenesis depend on Plk4 concentration, requiring the matrix that surrounds centrioles.
This study presents a new accretion model for spontaneous microtubule formation. In this model, microtubules form through a multitude of pathways and sheet-like oligomeric intermediates in a process akin to crystal growth.
Culver and Mariappan show newly synthesized tail-anchored (TA) proteins are polyubiquitinated and yet are targeted properly, deubiquitinated, and inserted into the ER. The ER-localized deubiquitinases USP20/33 remove TA ubiquitin modifications. Without USP20/33, ubiquitinated TAs accumulate in the ER membrane.
How lipid droplets are formed is largely unclear. Chen et al. show that FIT2 recruits ER tubule-forming proteins and septin cytoskeletons to facilitate nascent LD formation by providing membrane curvature and bulging scaffold.
VPS13D mutations result in severe mitochondrial defects. Guillén-Samander et al. show that VPS13D binds VAP in the ER and interacts with Miro on mitochondria and peroxisomes, where it could provide a bridge for lipid transport between these organelles.
The VPS13 proteins (VPS13A–D) are thought to mediate lipid transport between organelles and are linked to distinct neurological disorders in humans. Baldwin et al. found that, in addition to known involvement in mitochondrial morphology, VPS13D is essential for peroxisome biogenesis.
Tordonato et al. reveal miRNA-146 as a specific marker for breast stem cells and for cancer stem cells. miR-146 maintains the stem cell identity and coordinates a transcriptional and metabolic program, distinct from bulk cells, connected to the refractoriness to antifolate drugs.
Rabanal-Ruiz and Byron et al. present a novel mechanism of nutrient signaling that identifies FAs as key cellular hubs that coordinate growth factor signaling and amino acid input into the cell and are required for efficient downstream activation of mTORC1.
Dünkler et al. discover that the subunit Pea2 recruits type V myosin Myo2 to the yeast polarisome. Experimental evidence and biophysical modeling indicate that this interaction generates an actin-dependent force to physically compact and thus spatially focus the polarisome and to mold the bud into its characteristic pointed shape.
Yan et al. identify C. elegans RTKN-1 as a novel endocytic recycling regulator that impedes UNC-60A/cofilin-mediated endosomal actin disassembly. Further evidence indicates that the self-binding capacity of RTKN-1 is indispensable for this functionality and SDPN-1/Syndapin acts to direct the proper residency of RTKN-1 in recycling endosomes.
Monster, Donker, et al. demonstrate how epithelial cells can round up as they enter mitosis while still maintaining the integrity of the epithelial barrier. This requires an asymmetric composition of mitotic cell–cell junctions, which is established through an E-cadherin mechanoresponse in neighbors of mitotic cells.
Postsynaptic development requires the Frizzled nuclear import (FNI) pathway entailing the internalization and subsequent cleavage of Frizzled-2. Kim et al. show that Drosophila ALS2 regulates postsynaptic development by directing Frizzled-2 trafficking to late endosomes, where the Frizzled-2 C terminus is cleaved, and also promotes neuronal survival independently of the FNI pathway.
Presynaptic precursors deliver synaptic proteins to nascent and growing synapses. The authors provide evidence that during an early precursor formation step, the small GTPase Rab2 regulates immature precursors formation at the trans-Golgi prior to subsequent Arl8-dependent maturation steps.
Wood et al. use EM to visualize cytonemes, the specialized filopodia that mediate cell–cell signaling. Cytonemes of Drosophila cells have regions defined by oscillating diameters and contents that include ER, mitochondria, and ribosomes. Cytonemes contact target cells by penetrating into invaginations of target cell membranes.
May et al. combine proximity labeling with quantitative mass spectrometry to profile the proteome of primary cilia in cells responding to Hedgehog. They identify signaling factors that undergo dynamic ciliary enrichment and uncover an unanticipated regulation of ciliary cAMP signaling.
Marenda et al. introduce a parameter-free algorithm to quantify super-structures and connected clusters in SMLM datasets. The algorithm is tested on simulated and experimental datasets, demonstrating that it can be used as an unbiased tool to extract information beyond simple clustering.