Issues

Margarete M.S. Heck, professor of cell biology and genetics, University of Edinburgh, died peacefully at home amid her loving family under a blue moon on August 30, 2023, after a long journey with ovarian cancer.

Metabolic plasticity of neurons ensures their activity continues when glucose is limited. Walsh and Simon discuss new work by Ashrafi and colleagues that finds Sirtuin 3 directs local metabolic adaptation at synapses during sustained glucose deprivation.

Cooper discusses work from the Di Pietro group demonstrating that multiple CPI-motif proteins play distinct synergistic and antagonistic roles in actin assembly.

Jin and Worman discuss work from Hasper and colleagues, who discovered that turnover of lamin A/C and progerin is substantially slower specifically in disease-afflicted tissues.

Lyu et al. summarize the current knowledge of multiciliogenesis by which the respiratory tract, brain ventricles, and reproductive tracts of vertebrates form multiple motile cilia for tissue homeostasis.

Peglion and Etienne-Manneville discuss new insights into the pleiotropic effects of cell polarity alteration in cancer pathophysiology.

Mutations in many broadly expressed proteins cause diseases that manifest only in specific tissues. We show that the mutation that causes Hutchinson–Gilford progeria syndrome slows lamin A/C protein turnover in disease-afflicted tissues, causing the mutant protein to accumulate over time. Effective therapies for HGPS will need to surmount the long lifetime of progerin.

Neurons in the brain frequently experience glucose shortage and utilize oxidative fuels instead. Here, the authors demonstrate that glucose deprivation drives neuronal expression of the mitochondrial deacetylase sirtuin 3, which stimulates oxidative ATP synthesis in hippocampal nerve terminals to sustain neurotransmission.

Wu et al. show that the mitotic kinesin CENP-E promotes full expansion of the outer layer of the kinetochore known as the fibrous corona. This new function of CENP-E is independent of its motor activity. The findings expand the roles of CENP-E in spindle assembly and chromosome congression in mitosis.

Forte et al. report simulations revealing that bridging condensins are important to condense chromosomes into mitotic cylinders. This work underscores the importance of the bridging, as well as looping, activity of condensins, and points to a mechanistic model for chromatin structure at chromosome fragile sites.

Ochoa et al. show that vinculin, an actin-binding protein, strengthens the apical pole of embryonic stem cells in the neural tube so that they can perform vital tasks for their cell cycle, such as interkinetic nuclear migration and centrosome internalization.

Müller et al. uncover a role for septin sumoylation. Sumyolated septins recruit the Fir1-Skt5 complex to the septin hourglass. During cytokinesis, Fir1-Skt5 is released from the septins into the newly created space between the two rings. There, Fir1-Skt5 stimulates chitin synthase III for septum formation.

Kovács et al. report that the lipid transporter OSBP regulates apicobasal cargo sorting. By regulating PI(4)P and cholesterol concentrations in the TGN, OSBP controls sorting and subsequent cargo trafficking. Thus, lipid exchange by OSBP is indispensable for the polarized epithelial phenotype.

Proteins can target subsets of lipid droplets (LDs), but how this is mechanistically achieved is unclear. Here, Speer et al. characterize the protein triglyceride (TG)-associated lipid droplet protein 1 (Tld1) and dissect why it targets TG-rich LDs, as well as how it influences yeast lipolysis.

The EGFR–ERK pathway is one of the most important signaling cascades in cell survival and proliferation. The study reports that CDK2 regulates the ERK pathway via USP37. Importantly, combined CDK1/2 and EGFR inhibitors have a synergetic anticancer effect through the downregulation of ERK1/2 stability and activity.

Li et al. demonstrate a role of Kinesin-1 in cortical organization in Drosophila embryos. Kinesin-1 controls segregation of EB1 and Patronin/Shot to caps, and Rho signaling and Par-1 to the intercap region. This cortical pattern may be maintained by mutual antagonism of Par-1 and Patronin/Shot.

Altas et al. demonstrate that astrocytic ion channel proteostasis coordinated by an E3 ubiquitin ligase Nedd4-2 is of particular importance for the maintenance of neuronal network activity.

Actin capping protein localization at yeast endocytic sites was believed to depend on its ability to bind the actin filament barbed end. Lamb et al. show that three proteins containing actin capping protein–interacting motifs mediate recruitment and turnover of capping protein at yeast endocytic sites.

Our understanding of subcellular machinery is often inferred from that of cultured cells. Hutchison et al. have generated a tricolor tunable reporter mouse for simultaneous imaging of lysosomes, mitochondria, and microtubules in the native tissues at a single-cell resolution.

Application of the subpixel resolution membrane contact site (MCS) detection algorithm, MCS-DETECT, to 3D STED super-resolution image volumes identifies novel dual control of tubular riboMERCs, whose formation is dependent on RRBP1 and size modulated by Gp78 E3 ubiquitin ligase activity.