Issues

Dario Altieri discusses the life and achievements of Filippo Giancotti, who passed away on July 14, 2023.

Weckerly and Hammond discuss the identification of the first truly sensitive biosensor for an enigmatic signaling lipid, PI(3,5)P₂, by Vines et al.

Jason Brickner highlights work from Kumar and colleagues demonstrating that Nup170 regulates chromatin silencing through the Ctf18-RFC complex, establishing PCNA levels on DNA.

Subramani et al. review the shared and unique mechanisms of peroxisomal and mitochondrial division and their dependence on subcellular organelles.

Zhang, Medwig-Kinney, and Goldstein show through live-cell imaging of endogenously tagged proteins that the medioapical actomyosin network driving apical constriction during C. elegans gastrulation is organized diffusely, with a mixed-polarity actin filament network, in contrast to the sarcomere-like architecture previously observed in the Drosophila ventral furrow.

Kumar et al. report that the yeast nucleoporin Nup170 regulates chromatin silencing through the Ctf18-RFC, an alternative PCNA loader, to establish PCNA levels on DNA in a cell cycle–regulated manner. Increasing PCNA levels by removing Elg1 restores silencing defects. They ascribe this chromatin silencing function to a subset of NPCs.

Lee et al. show that the inner nuclear membrane (INM) of animal cells harbors a unique lipid composition that is under local control by CTDNEP1/lipin1. An amphipathic helix in the resident INM protein Sun2 senses local changes in lipids and contributes to its INM retention.

Lewis et al. reveal that herpes simplex virus infection alters the heterochromatin landscape of the host to support the egress of progeny out of the nucleus. This work elegantly demonstrates that host chromatin architecture, beyond transcriptional regulation, is a critical structural component in virus-host interactions.

This study shows that mammary gland branching morphogenesis is orchestrated by spatiotemporally coordinated changes in tip cell motility and proliferation to alternate between branch elongation and branch point formation.

Myronidi et al. report that the ER-membrane chaperone Shr3 specifically guides the co-translational folding of amino acid permeases with 12 membrane-spanning segments (MS). Shr3 transiently engages with N-terminal MS, acting as a structural scaffold that facilitates the folding of C-terminal MS as translation proceeds to completion.

Organisms are adapted to daily cyclic environmental changes thanks to the circadian clocks located in all their cells and tissues. This study shows that mechanosensing severely affects circadian rhythms at the single-cell level through alterations in the expression and intracellular localization of transcriptional regulators YAP/TAZ.

Caveolins are membrane-shaping proteins driving the formation of plasma membrane caveolae by gradually oligomerizing while trafficking through the biosynthetic-secretory pathway. This work describes intricate proteostasis mechanisms that actively regulate newly synthesized caveolins to balance anterograde trafficking and proteasomal degradation to ensure oligomeric assembly and prevent toxic aggregation.

Boutry et al. show that Arf1-PI4KIIIβ positive vesicles participate in the fission of lysosomal tubules through lysosomal PI(3)P regulation. This work identifies new components involved in the scission of lysosomal tubules and demonstrates that this process requires an exquisite regulation of phosphoinositides on lysosomes.

PTEN is a lipid phosphatase that plays an important role in cancer and aging in mice. Zhang et al. show that PTEN regulates chaperone-mediated autophagy (CMA) and is itself a CMA substrate. Several metabolic changes downstream of PTEN require CMA activity.

Polydom is an extracellular matrix protein involved in lymphangiogenesis. Sato-Nishiuchi et al. demonstrate that Polydom binds directly to Tie1, an orphan receptor in the Angiopoietin–Tie system, thereby facilitating lymphatic endothelial cell migration as an essential step in lymphatic vessel remodeling.

Kol et al. identify CLPTM1L as a novel component of the GPI-anchoring pathway and show that it is targeted by HCMV. This discovery sheds light on basic aspects of cell biology, as well as on the sophistication with which viruses manipulate the immune response.

A kinesin-4–mediated, selective inhibition of microtubule growth at antiparallel overlaps suppresses encounters between antiparallel microtubules in the unipolar microtubule array in tip-growing moss cells. This mechanism constitutes a new organizing principle within unipolar microtubule arrays.

GstO1 postsynaptically suppresses the growth of the Drosophila neuromuscular junctions by inhibiting the BMP signaling pathway. GstO1 interacts with Gbb and prompts its glutathionylation. E3 ligase Ctrip binds glutathionylated Gbb and facilitates its proteasome-mediated degradation, indicating a crosstalk between glutathionylation and ubiquitination in regulating Gbb homeostasis.

Dudka et al. present a fully automated computational pipeline detecting statistical signatures of evolutionary innovation in rodents, primates, carnivores, birds, and flies. The manuscript provides examples showing how these analyses can guide hypotheses and experimental design to gain insights into the regulation of protein function.

In this work, the authors describe a new biosensor for the phosphoinositide signaling lipid PI(3,5)P₂. They demonstrate that this reporter faithfully reports PI(3,5)P₂ dynamics in both Dictyostelium amoebae and mammalian cells and uncover details of how PI(3,5)P₂ formation is regulated during phagosome maturation.