Issues

Gaia Pigino studies the molecular mechanisms and principles of self-organization in cilia using 3D cryo-EM.

Morao and Ercan highlight work from Belew and colleagues that reveals how germ cells repress transcription during nutrient starvation.

King discusses work from the Machesky laboratory that identifies CYRI-A as a novel regulator of macropinocytosis that resolves macropinosome formation by locally sequestering active RAC1.

Gaudin et al. discuss work from the Reiter laboratory demonstrating that the DISCO complex initiates ciliogenesis by restraining centriole length and assembling distal appendages.

Tavernier et al. review the different activation mechanisms of the Aurora A kinase during mitotic entry and progression.

Borchers et al. review regulatory principles in the activation of endocytic Rab GTPases and how they apply to other Rab and Arf GTPases.

Gan outlines mitochondrial functions in driving ferroptosis and discusses mitochondria-localized defense systems that quench mitochondrial lipid peroxides and suppress ferroptosis.

Bomba-Warczak et al. use stable isotope labeling of mice and tandem mass spectrometry to discover a pool of mitochondrial proteins persisting for months in tissues containing postmitotic cells. Long-lived proteins are enriched at cristae. Crosslinking analysis revealed limited exchange of subunits throughout their lifetime.

Cowell et al. show that talin rod domain–containing protein 1 (TLNRD1), a protein with homology to the central region of the integrin regulator, talin, has retained the diverse interactions of talin R7R8 but has developed distinct functionality as an actin-bundling protein that promotes filopodia assembly.

Belew et al. report that C. elegans primordial germ cells become transcriptionally repressed if embryos hatch without nutrients. They also describe a novel pathway whereby condensin II and TOP-2 regulate heterochromatin to compact the germline genome to globally repress transcription.

Extracellular vesicles (EVs) may mediate intercellular communication through the transfer of cargo molecules. Song et al. report that cyclin D1 is sorted into EVs during neuronal differentiation and that these EVs help to promote the neural induction of embryonic stem cells.

The assembly of the γ-secretase complex is coordinated by prior formation in the ER of dimeric subcomplexes, which next independently exit the ER. This mechanism could both prevent premature assembly and help the maintenance of stoichiometric levels of γ-secretase subunits during the assembly process.

Tethering proteins at ER–plasma membrane contacts may have specific functions in addition to tethering. This study shows that the yeast TMEM16 tethering protein Ist2 recruits the phosphatidylserine-transporting proteins Osh6 and Osh7 to ER–PM contacts, with this interaction being required for aminophospholipid metabolism in the absence of the phosphatidylserine decarboxylase PSD1.

Ho et al. provide a novel insight on how loss of TDP-43 (a major disease protein) leads to SREBF2 (a key regulator)–dependent disruption of cholesterol metabolism, which in turn affects myelination. Their results further implicate that disturbance of cholesterol metabolism may be involved in ALS, FTD, and TDP-43 proteinopathies–related disease.

Le et al. implicate CYRI-A in resolving macropinosome formation by locally sequestering active RAC1. They further show that CYRI-mediated macropinocytosis contributes to integrin internalization, impacting spreading and invasion of cancer cells.

Phagocytes engulf particles into phagolysosomes for degradation. However, the ultimate fate of phagolysosomes is undefined. Lancaster, Fountain, et al. show that phagosomes fragment to reform lysosomes in a clathrin-dependent manner. This process helps maintain the degradative capacity of phagocytes for subsequent rounds of phagocytosis.

Chang et al. report that the inflammatory bowel disease risk gene INAVA responds to the inflammatory cytokine IL-1β to form cytosolic biomolecular condensates that rapidly assemble and physiologically resolve. The condensates contain ubiquitin and the E3 ligase βTrCP2, implicating function in regulation of cellular proteostasis.

Puri et al. demonstrate that the Kinesin-13 family microtubule catastrophe factor is a critical determinant of neuronal microtubule dynamics and polarity. This work provides a mechanistic link between Wnt signaling and Kinesin-13 in establishing microtubule polarity in touch neurons of C. elegans.

Obliteration of the paracellular space at tricellular contacts is crucial for the full barrier function of epithelia. This study shows that a tricellular tight junction–associated membrane protein, angulin-1, rather than tricellulin, is essential for the plasma membrane seal at tricellular contacts in vertebrate epithelial cells.

Kumar et al. identify a multiprotein complex called DISCO (distal centriole complex) required to nucleate distal appendages and restrain centriole elongation, which are essential for the initiation of cilium assembly. Without DISCO, cells fail to ciliate and transduce Hedgehog signals, which are critical for mammalian development.

At the basal state, the ciliary levels of Smo are kept low through the actions of a ciliary localized E2 ubiquitin–conjugating enzyme, Ube2l3, and an E3 ubiquitin ligase, Wwp1. Pathway activation leads to removal of Wwp1 from cilia, allowing Smo to accumulate in cilia and become activated.

Zhou, Vachon, et al. identify HSPG Syndecan as a novel core organizer of the cholinergic synapse in C. elegans. Syndecan/SDN-1 acts by bridging extracellular matrix components with intracellular scaffolding proteins to recruit alpha7-like acetylcholine receptors at postsynaptic sites.

Trillet et al. report that the glycoprotein GP130 orchestrates the availability of the G protein–coupled receptor for apelin APLNR at the plasma membrane of glioblastoma stem-like cells, thereby modulating APLN signaling toward self-renewal. By modulating ELMOD1 expression, GP130 ultimately tunes ARF-mediated endovesicular internalization and recycling.

Crossley et al. demonstrate that GFP-tagged, catalytically inactive RNase H1 protein is a versatile tool for imaging cellular R-loops. They also show that it is significantly more specific than the commonly used S9.6 antibody, which detects considerable nonspecific signal.

Shi, Li, et al. report the development of label-retention expansion microscopy (LR-ExM) with a set of trifunctional anchors that not only prevent fluorescent signal loss but also enable high-efficiency labeling using SNAP and CLIP tags.

Ronchi et al. present a workflow to facilitate precise targeting for volume EM (vEM) acquisitions. This method allows ultrastructural visualization of single cells within a millimeter-range specimen based on molecular identity characterized by fluorescence.

Bourke et al. present a new method for using light to trigger protein trafficking through the secretory network. They use the method to characterize how synaptic proteins traffic from different subcellular domains in neurons.