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Amol Ugale, Dhanlakshmi Shunmugam, Lokesh G. Pimpale, Elisabeth Rebhan, Manuela Baccarini
Ugale et al. demonstrate that CDC42, ERK, and mTORC1 signaling are polarized in premitotic hematopoietic stem cells and unequally segregated during asymmetric cell division. A CDC42/ERK/mTORC1 pathway maintains HSC polarity and balances symmetric and asymmetric cell division.
Article
Adi Shimshon, Karin Dahan, Mor Israel-Gueta, Diana Olmayev-Yaakobov, Richard T. Timms, Aizat Bekturova, Yaara Makaros, Stephen J. Elledge, Itay Koren
How are mislocalized secretory proteins targeted for destruction? Shimshon, Dahan, et al. discover that DPP8/9 peptidases expose a hidden “destroy me” tag in the targeting signal of substrates upon translocation failure, which flags them for UBR E3 ligases-mediated breakdown, preserving cellular protein balance.
Report
Lila Neahring, Nathan H. Cho, Yifei He, Gaoxiang Liu, Jonathan Fernandes, Caleb J. Rux, Konstantinos Nakos, Radhika Subramanian, Srigokul Upadhyayula, Ahmet Yildiz, Sophie Dumont
The anaphase spindle exhibits left-handed twist, but the source of this chirality is unknown. Neahring et al. identify two spindle motors that promote twist but find that the spindle positioning machinery counteracts it, revealing that twist is set by factors within and outside the spindle.
Report
Anja Göder, Chrystelle Antoinat Maric, Michael D. Rainey, Aisling O’Connor, Chiara Cazzaniga, Daniel Shamavu, Jean-Charles Cadoret, Corrado Santocanale
In human cells, the S-phase-promoting kinase CDC7 exists in two alternative complexes: CDC7-DBF4 or CDC7-DRF1. Here, Göder et al. show that while CDC7’s essential function can be supported by both subunits, DBF4 is the primary mediator of CDC7 activity during DNA replication.
Article
Shariq S. Ansari, Miriam E. Dillard, Yan Zhang, Mary Ashley Austria, Naoko Boatwright, Elaine L. Shelton, Daniel P. Stewart, Amanda Johnson, Christina E. Wang, Brandon M. Young, Zoran Rankovic, Baranda S. Hansen, Shondra M. Pruett-Miller, Alexandre F. Carisey, John D. Schuetz, Camenzind G. Robinson, Stacey K. Ogden
This study reveals crosstalk between Sonic Hedgehog (SHH) and prostaglandin signaling pathways. SHH signaling leads to the secretion of PGE2, which activates the ciliary EP4 receptor to promote primary cilium length stability. Disruption of SHH-to-EP4 communication leads to primary cilium shortening and reduced SHH signal output.
Article
Erica C. Dresselhaus, Kathryn P. Harris, Cassandra R. Blanchette, Kate Koles, Steven J. Del Signore, Matthew F. Pescosolido, Biljana Ermanoska, Mark Rozencwaig, Rebecca C. Soslowsky, Michael J. Parisi, Bryan A. Stewart, Timothy J. Mosca, Avital A. Rodal
ESCRT depletion disrupts synaptic extracellular vesicle (EV) release without affecting signaling by several EV cargoes. EVs are phagocytosed by adjacent cells, and ESCRT disruption causes compensatory autophagy. These results suggest that EV release serves proteostatic rather than intercellular signaling functions for these cargoes at synapses.
Report
Sophie Gray, Cecile Fort, Richard John Wheeler
We used high-frame-rate, dual-color fluorescence microscopy to visualize IFT trafficking in the beating flagella of Leishmania mexicana, a uniflagellate human parasite. This revealed differing sensitivity of IFT train speed to genetically induced, mechanical, and natural changes in beating.
Issue Cover
Current Issue
Volume 223,
Issue 6,
3 June 2024
Reviews & Opinions
Perspective
Ivan R. Nabi, Ben Cardoen, Ismail M. Khater, Guang Gao, Timothy H. Wong, Ghassan Hamarneh
Nabi and colleagues discuss supervision paradigms for biological discovery from super-resolution microscopy to enable AI-accelerated exploration of the nanoscale architecture of subcellular macromolecules and organelles.
Perspective
Anda Huna, Amélie Massemin, Gabriela Makulyte, Jean-Michel Flaman, Nadine Martin, David Bernard
Huna et al. provide insights into the shifting perception of cellular senescence: from a mere cell proliferation arrest to a reinforcement or change of cell identity.
Spotlight
G.W. Gant Luxton
G.W. Gant Luxton discusses new findings from the Roux group that show how changes in cellular GTP levels alter the rates of nucleocytoplasmic transport.

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