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Lepeta et al. design a novel approach, using nanobody-based protein binders, to phosphorylate a chosen GFP fusion protein target by a defined kinase in vivo in a tissue-specific manner. They show detailed characterization and validation of two engineered kinases, based on ROCK and Src.

Dua et al. develop a novel system to induce mitochondrial DNA (mtDNA)-specific damage, avoiding pleiotropic perturbation to the nuclear genome. Using this system, their study provides unique insights into the consequences of mtDNA damage on mitochondrial dynamics and pathways involved in regulating the same.

Article

Atherton and Konstantinou et al. reveal the molecular mechanisms underpinning an interaction between the integrin-associated proteins tensin3 and talin. By associating with the intracellular force-generating actomyosin machinery, this talin–tensin3 interaction drives the formation of fibrillar adhesions and associated fibronectin fibrils as part of the extracellular matrix remodeling.

Li et al. identify VAMP4 as a regulator for controlling insulin levels and reveal that VAMP4 participates in insulin granule trafficking by assembling a SNARE complex with STX7, STX8, and VTI1B on lysosomes to maintain insulin homeostasis in β cells.

ARL3 mutations disrupt protein import into cilia causing Joubert syndrome (JBTS). Using Chlamydomonas, Liu et al. show that ARL3 recruits the BBSome to pass the transition zone for ciliary retrieval, providing a mechanistic explanation for why JBTS phenotypically overlaps with Bardet-Biedl syndrome.

Gaurav et al. report impaired recycling of the McLeod syndrome protein XK from Rab11-positive recycling endosomes to cell surfaces for transporting manganese in Huntington's disease striatal cells, thus providing a mechanism for the similarity in the preferential degeneration of striatal neurons between these two diseases.

Endocytosis is composed of early and late phases. This study demonstrates that the yeast Eps15/Pan1p is a key regulator for the late phase, and ectopic targeting of Pan1p to the peroxisome triggers most of the events occurring during the late phase at the peroxisome.

Calvi et al. identify PP1 protein phosphatases as regulators of cell polarity in Caenorhabditis. elegans embryos. Their results show that two phosphatases, GSP-1 and GSP-2, interact with the polarity protein PAR-2 and control its localization and polarity establishment.

Dai et al. show that the loss of ARL13, a small GTPase already known for its role in ciliary protein import, also impairs the export of membrane-associated proteins from Chlamydomonas cilia via the BBSome pathway. Thus, ARL13 and BBSome deficiencies lead to overlapping defects in ciliary membrane composition.

Shrivastava et al. demonstrate that the function of sHsp sequestrase is evolutionarily conserved and based on specific sequence features of their disordered N-terminal extensions. The sHsps sequestrases of C. elegans fulfill cytoprotective functions and contribute to lifespan extension in long-lived daf-2 mutant animals.

Park, Kim, Cho, et al. show that actin-regulatory Vav-Rac1-SCAR signaling independently regulates structural and functional presynaptic plasticity by driving BMP macropinocytosis and degradation of BMP receptors and mobilization of the reserve synaptic-vesicle pool, respectively. This work suggests that Vav differentially regulates distinct presynaptic actin pools with highly specialized tasks.

Sosicka et al. show that cells assess the metabolic origin of fucose for glycosylation and selectively use activated GDP-fucose from multiple, separate pools. Organelles, fucosyltransferases, and individual glycoproteins show different preferences, dispelling the concept of a single, homogenous precursor pool.

Lysosomes are dynamic organelles requiring proper regulation. Wong et al. demonstrate that inter-lysosomal untethering events are driven by mitochondria–lysosome contact sites, which couple together Drp1 and Rab7 GTP hydrolysis machinery via a mitochondrial Mid51/Fis1 oligomerization complex, which is differentially modulated by distinct disease-associated Mid51 mutants.

Report

Ohshima et al. demonstrate that the iron-storage protein ferritin undergoes liquid–liquid phase separation, which is mediated by multivalent interactions with NCOA4. Ferritin–NCOA4 condensates are subjected to macroautophagy and endosomal microautophagy and delivered to lysosomes to release iron ions.

Review

Wenzel et al. review how the endoplasmic reticulum controls the positioning, dynamics, and functions of other organelles via membrane contact sites.

Spotlight

André Barros-Carvalho and Eurico Morais-de-Sá highlight work from Calvi and colleagues that demonstrates a role for PP1 in establishing embryo polarity via regulation of PAR-2 localization.

Marsan and Huang discuss work from Chhetri et al. demonstrating that mutant huntingtin interferes with XK surface recycling and reduces divalent ion transport across the membrane.

Wang and Zhang preview work from the Mizushima lab showing that NCOA4 mediates formation of ferritin condensates that are destined for degradation by macroautophagy and microautophagy.

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