People & Ideas
We interviewed our Early Career Advisory Board to learn about their experiences finding their academic position and managing a new laboratory, and their views on peer review and scientific publishing.
Linda Wordeman discusses work from Strothman et al. that sheds new light on the differences between plus- and minus-end microtubule dynamics.
Li and Monk preview new work from Elazar and colleagues that demonstrates that coordination of internodal and paranodal cell adhesion factors is necessary for regulation of myelination.
Mozzetta and Tedesco preview work from the Murry laboratory yielding insight into cardiac laminopathy pathogenesis mechanisms by analyzing chromatin compartment dynamics in a haploinsufficient model of the disease.
Branching microtubule nucleation by its molecular mediators has never been directly observed in animal cells. By imaging augmin, γ-TuRC, and microtubules with high spatiotemporal resolution, Verma and Maresca quantitatively define the sequential steps of augmin-mediated branching microtubule nucleation in dividing Drosophila cells.
Dynamic microtubule minus ends are more stable than plus ends when controlling for growth rate. Strothman et al. find that minus-end stability is not determined by the size of the stabilizing GTP cap, but rather the GTP-tubulin off-rate. Furthermore, the mitotic kinesins MCAK and HSET antagonistically regulate minus-end catastrophe by modulation of the tubulin off-rate.
Costa and Ohkura provide new insight into how the bipolar spindle is stably maintained during metaphase arrest in oocytes. They find that many important spindle proteins change their localization during arrest in Drosophila oocytes and show the importance of these changes in stabilizing the spindle during arrest.
The essential kinase CHK1 controls cell cycle checkpoint signaling and S-phase progression. Michelena et al. reveal that steady-state activity of CHK1 is required to sustain its own stability and that failure to do so results in CHK1 degradation and sensitizes cells to replication stress.
Retromer sorts diverse membrane proteins into recycling tubules/vesicles from the endosome. How it precisely selects its cargos is not well described. Suzuki et al. reveal that retromer interacts with a bipartite sorting signal, which facilitates precise cargo recognition.
Elazar et al. show that reduced axoglial adhesion at both the paranodal junction and the internodes results in the formation of multimyelinated axons. Their findings demonstrate that accurate ensheathment by oligodendrocytes depends on the coordinated action of these different adhesion systems.
Palmer et al. identify NRF1 as a novel CDK2 interactor and substrate. This interaction was found to be important for the DNA-binding activity of NRF1. Their findings demonstrate that the loss of CDK2 expression impairs the regulation of NRF1 transcriptional activity, leading to inappropriate transcription during meiotic division.
Bertero et al. observe that lamin A/C haploinsufficiency in human cardiomyocytes markedly alters electrophysiology, contractility, gene expression, and chromosomal topology. Contrary to expectations, however, changes in chromatin compartments involve just few regions, and most dysregulated genes lie outside these hotspots.
Ben-Yishay et al. measure the interactions of the mRNA export factor NXF1 with NPC components in individual nuclear pores in intact human cells and show that NXF1 functions on the cytoplasmic side of the NPC for the release of mRNA into the cytoplasm.
Hook3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein-1 and KIF1C
Intracellular transport can be driven by unidirectional motors acting in opposing directions, but how bidirectional transport of cargo is regulated is unclear. Kendrick et al. show that the dynein-activating adaptor Hook3 interacts with the opposite-polarity motors cytoplasmic dynein-1 and the kinesin KIF1C. In vitro, Hook3 can scaffold both motors for bidirectional motility on microtubules.
The BH3-only pro-apoptotic protein BIK is regulated by the ubiquitin–proteasome system. Chen et al. identify ASB11 as an E3 ligase for BIK ubiquitination and degradation and uncover different mechanisms that regulate ASB11 activity, and thus cell survival versus death, during ER stress and DNA damage responses. Blocking this degradative pathway may increase the efficacy of active BIK gene therapy as an anti-cancer therapy.
Retromer and TBC1D5 maintain late endosomal RAB7 domains to enable amino acid–induced mTORC1 signaling
Kvainickas et al. establish that retromer, a coat complex that promotes endosomal recycling, is also required for the activation of the lysosomal mTORC1 complex. Mechanistically, retromer and the retromer-associated protein TBC1D5 separate mTORC1 and RAB7 microdomains on late endosomes, which is necessary for amino acid–mediated mTORC1 activation.
Borrelia burgdorferi is the causative agent of Lyme disease. Klose et al. show that SNX3 drives processing of internalized B. burgdorferi by binding PI(3)P on the phagosome surface and recruiting galectin-9 vesicles, thus forming a convergence point for the endosomal recycling machinery during processing of spirochetes.
SRC and ERK cooperatively phosphorylate DLC1 and attenuate its Rho-GAP and tumor suppressor functions
DLC1 controls focal adhesion dynamics and other processes that suppress tumorigenesis; therefore, it is unclear why some cancers maintain high levels of DLC1. Tripathi et al. show that phosphorylation of DLC1 by SRC and ERK mitigates DLC1’s tumor suppressor activities but these can be reactivated by kinase inhibition as a potential cancer treatment.
Azoitei, Noh, et al. engineer fluorescent biosensors to measure activation at the subcellular level and with subsecond kinetics of GEF-H1, a Rho GTPase that regulates cytoskeletal dynamics. In combination with computational image time series analysis, the biosensors reveal the synergistic role of microtubule dynamics and Src phosphorylation in regulating GEF-H1 activity locally during cell migration.
Precise levels of collagen IV dictate the mechanical and signaling functions of basement membranes (BMs), but how collagen is incorporated into BMs in vivo is unclear. Jayadev et al. identify distinct integrin-based mechanisms controlling BM collagen levels in Caenorhabditis elegans.
Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
This study shows that Pkc1 inhibits yeast pheromone signaling upon intrinsic and extrinsic mechanical stress. Pkc1 phosphorylates the RING-H2 domains of the scaffolds Ste5 and Far1, thereby preventing their interaction with Gβγ at the plasma membrane. This crosstalk mechanism regulates polarized growth and cell–cell fusion during mating.
Saw et al. show via the combinatorial deletion of Timp family members in mice that metalloprotease regulation of FGF-2 is a crucial event in the chondrocyte maturation program, underlying the growth plate development and bone elongation responsible for attaining proper body stature.
O’Shaughnessy et al. present new software called ImageTank to process lattice light-sheet images of FRET biosensors. ImageTank efficiently handles large 3D datasets and includes tools for visualization and analysis. Its capabilities are demonstrated using a new Rap1 biosensor in motile cells.