Issues

Laura Machesky highlights work from David Sherwood’s group that shows a new role for de novo lipid synthesis and prenylation polarization in invasive protrusion construction.

Anbing Shi discusses new work from Li and colleagues revealing that LYSMD proteins facilitate the development of lysosome-related organelles by activating Rab32-family GTPases.

Tromm and Milovanovic highlight two recent studies that reveal how condensate formation by synaptotagmin-1 controls calcium-triggered synaptic vesicle exocytosis.

This work shows that activation of the integrated stress response (ISR) with orally available and clinically approved GCN2 activator halofuginone reduces diabetes-like phenotypes in a mouse model of diet-induced obesity. Conversely, ISR inhibition aggravates glucose intolerance in obese mice. This demonstrates the therapeutic value of increasing ISR signaling in diabetes.

Chen et al. delineate a novel mode of mitochondrial migration by “hitchhiking” on ER via the protein tether pair between mitofusins (MFNs) and REEP5. This dynamic association facilitates mitochondrial distribution and maintains oxidative homeostasis, which provides additional insights into the mechanism and functions of ER–mitochondria contacts involving MFNs.

The two-pore leak K⁺ (K2P) channels TRAAK and TREK-1 repolarize membrane potential at nodes of Ranvier. Escobedo et al. identify an evolutionarily conserved, AnkyrinG-dependent motif in TRAAK, necessary and sufficient for clustering these channels at nodes of Ranvier and axon initial segments.

T cells form focal adhesions consisting of integrins, talin, and vinculin when migrating on extracellular matrix proteins. Like mesenchymal cells, these adhesions are sites of contractile force transmission, and T cells use them to facilitate their navigation through complex environments.

Salvador-Garcia and colleagues combine Drosophila genetics, biochemistry, and biophysics to dissect the functions of the dynein motor. They reveal organismal effects of human disease-associated mutations and provide evidence for a non-canonical role for dynein in anaphase progression that involves it operating in a specific load regime.

Riggs et al. characterize the RNA binding protein Ubiquitin Associated Protein 2-Like (UBAP2L) and its role in stress-responsive biomolecular condensates, stress granules and p-bodies. They find that UBAP2L contributes to PB biogenesis and SG–PB interactions, in addition to SG formation.

In the syncytial Drosophila embryo, nascent actin caps form as local collections of plasma membrane folds and tubules. The centrosome is required for these plasma membrane infoldings and for recruiting Arp2/3 actin networks that reconfigure the membranes for cap growth.

Cdc42 regulates growth in most eukaryotes and must be cyclically activated and inactivated at sites of growth. We show that endocytosis allows inactivated sites to regain activity by removing the negative feedback (Pak1 kinase) from cell ends.

The E3 ligase RNF146 regulates peroxisomal-protein import by preventing the PARsylation of peroxisomal proteins by the poly-ADP ribose polymerases TNKS and TNKS2. Highlighting the specialization of cell-wide regulatory mechanisms at organelles, peroxisomal recruitment of TNKS/2 reorients TNKS/2 activity away from components of the Wnt/β-catenin pathway.

Calorie restriction increases lifespan. It is unclear how calorie restriction alters gastrointestinal cell composition. This study finds that calorie restriction promotes gastric endocrine cell differentiation through active Notch signaling and that the transcription factor FOXO1 regulates this process.

Brombacher et al. study the role of AMP-activated kinase in tolerance induction by dendritic cells (DCs). They find that AMPK activation promotes DC tolerogenicity by increasing breakdown of glycerophospholipids, enhancing mitochondrial fission–dependent fatty acid oxidation, and upregulating glucose catabolism. This provides novel insights into the metabolic programs that control DC tolerogenicity.

Li et al. identify Caenorhabditis elegans and mammalian LysM domain–containing proteins as essential regulators of lysosome-related organelle (LRO) biogenesis. These proteins interact with guanine nucleotide exchange factors of Rab32 GTPases, promoting their activation and ensuring proper LRO formation in worms and melanoma cells.

Zhu et al. reveal that Synaptotagmin 1 (Syt1) forms condensate to interact with negatively charged lipid bilayers and recruit SNARE complexes and complexin. Syt1 undergoes a liquid-to-gel-like phase transition in condensates, reflecting the oligomerization of Syt1, which is blocked or reversed by Ca²⁺.

Invasive cells form large, specialized protrusions to break through basement membrane (BM) matrix barriers. Park et al. reveal a crucial requirement for de novo lipid synthesis and a dynamic polarizing prenylation system to rapidly construct invasive protrusions that breach BMs.

Before differentiating, cerebellar granule cell neurons require primary cilia to detect and proliferate in response to sonic hedgehog; however, mature granule cell neurons lack primary cilia. Here, Ott, Constable et al. describe in ultrastructural detail the pathway for postmitotic cilia deconstruction.

Detecting the activation of small GTPases within living cells is crucial for understanding cellular processes. We present a novel method, the Small GTPase ActIvitY ANalyzing (SAIYAN) system, for detecting the activation of endogenous small GTPases via fluorescent signals utilizing a split mNeonGreen system.

Here, we present a rapid and efficient LiAc/ssDNA/PEG protocol for transforming the polymorphic multibudding fungus Aureobasidium pullulans. Transformed strains reveal how multinucleate cells scale nuclear volume in this organism.

Lee and Gala et al. meta-analyzed studies identifying mRNAs localized to cytoplasmic projections of various mammalian glial cells, which they showed are strong predictors of localized RNA in Drosophila and are associated with neurological diseases. They found some are essential for synapse formation in adjacent neurons.