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Misfolded GPI-APs are released from the ER to the Golgi for rapid degradation in lysosomes by the constitutively active and stress-inducible RESET pathway. Using multiple complementary approaches, the authors demonstrate that competition by nascent glycoproteins for calnexin-binding promotes the release of misfolded GPI-APs for RESET.

Jones and Drummond et al. identify the C1 domain from the polarity kinase aPKC as a membrane recruitment module. Regulation of C1-mediated membrane recruitment by several other domains, including aPKC’s catalytic module, leads to polarized membrane targeting.

Quiescent naïve T cells patrol the body in a resting state, conserving energy and exhibiting slow transcription activity. However, when stimulated, they quickly increase nucleolar protein DCAF13 levels, facilitating nucleolar phase separation mediated by NPM1. This enhances ribosomal RNA maturation and boosts translational activity, supporting cell growth and proliferation.

Bingham et al. use bead-induced isolated presynapses and CRISPR-mediated tagging of endogenous actin in neurons coupled to super-resolution microscopy to reveal that presynapses contain distinct actin nanostructures: a faint mesh at the active zone, intrasynaptic rails, and perisynaptic corrals.

Mechanoreceptor cells develop delicate subcellular structures in their mechanosensory organelle (MO) for optimal mechanosensitivity. Song et al. analyze the ultrastructure of fly mechanosensory cilia and reveal that DCX-EMAP is a core structural organizer of fly MOs.

Zhu et al. use Drosophila gentics and cell imaging to show that different types of γ-tubulin complexes can be recruited to mitotic centrosomes via different molecular pathways, that these centrosomes can nucleate microtubules even when they fail to recruit γ-tubulin, and that the dynamic properties of microtubules appear to be influenced by how they are nucleated.

Smid, Garforth, et al. reconstitute pre-T cell receptor (preTCR) expression in non-immune cells to show that signaling is not required for its rapid internalization and degradation observed during T-cell development, and that the preTCR can drive tonic signaling in T cells.

It is unclear whether and how mitochondrial fusion is selected. In this work, Su et al. demonstrate that NME3 functions as a mitochondrial tethering complex via binding to phosphatidic acid derived from cardiolipin. NME3 thus selectively tethers mitochondria with externalized cardiolipin and promotes their fusion for functional homeostasis.

Lenhard, Gerlich et al. report in this study that the SARS-CoV-2 virus expresses the protein Orf9b to target the mitochondrial outer membrane receptor Tom70. Orf9b expression in human and yeast cells shows the strong potential of this viral protein to remodel the mitochondrial proteome.

Lin et al. report that Tejas, an essential component of piRNA pathway, plays a key role in recruiting Vasa (Vas) and Spindle-E through the distinct domains and contributes to the dynamics of Vas, thereby functioning for the proper assembly of nuage and for piRNA precursor processing.

Henkin, Brito, et al. reconstitute in vitro a functional module elucidating previously poorly understood mechanisms of poleward microtubule flux during eukaryotic cell division, reliant on the newly found inherent microtubule minus-end depolymerase activity of KIF2A, the major microtubule nucleator γTuRC, and a microtubule severing enzyme.


Gagliardi et al. develop a method to quantify spatio-temporal correlations in signaling. The code is open-source and available for R, Python, and as a napari plugin. They observe that oncogenic mutations in the MAPK/ERK and PIK3CA/Akt pathways of MCF10A epithelia hyperstimulate intercellular ERK activity waves.


Fuentes and Marin et al. show that Rtn4 forms linear-shaped oligomers containing an average of five Rtn4 proteins that localize to the sides of elliptical tubules with orientations parallel to the tubule axis. These oligomers increase local curvature in the ER membrane by increasing local Rtn4 density.

Wu et al. show that C17orf80 is a bona fide mitochondrial nucleoid protein, and that it acts to promote mtDNA replication. This work identifies a new player involved in regulating mtDNA maintenance and provides a potential target for treating human diseases associated with defective mtDNA metabolism.

Pedersen, Snoberger et al. measure the force sensitivity of the yeast endocytic myosin-1 called Myo5 and find that it is more likely to generate power than to serve as a force-sensitive anchor in cells. Implications for Myo5’s role in clathrin-mediated endocytosis are discussed.

Mitochondria are double membrane–bound organelles whose morphology and cellular distribution are controlled by the dynamic processes of fusion and fission. This study shows that mitochondrial fission, performed by the cytosolic dynamin-related protein Dnm1, requires the coordinated activity of a protein that localizes inside the organelle.


Lu and Gelfand preview work from Song et al., which reveals a role for the microtubule-binding protein DCX-EMAP in the 3D organization of mechanosensory organelles of Drosophila.

Westermann discusses two related studies examining a novel protein that plays a key role in mitochondrial division.

Ikeda et al. highlight work from Su and colleagues that describes the mechanism by which NME3 and phosphatidic acid promote mitochondrial tethering prior to fusion.

Activated T cells boost ribosome production to meet their enormous protein synthesis demands. Sharma and Shaw discuss work from Zhou et al. showing the protein DCAF13 mediates nucleolar expansion in this setting.

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