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Membrane trafficking is essential for organelle biogenesis. Here, the authors discover an alternative assembly of the Commander trafficking complex and show its role in melanosome biogenesis and in a subtype of albinism.

The receptor TLR9 needs to be carefully regulated to avoid recognition of self nucleic acids and ensuing autoinflammation. Saveanu and colleagues demonstrate a further level of regulation through the retention of TLR9 in IRAP⁺ endosomes.

Although effector activity and memory formation in CD8 + T cells are known to depend on mTORC1-mediated metabolic regulation, the molecular mechanisms involved are lesser known. Here authors show that NKG7, a lysosomal protein specifically expressed in CD8 + T cells, inhibits mTORC1 function via the lysosomal proton pump, vacuolar ATPase, promoting antitumor activity and expansion of memory T cell precursors.

Liu, Nie et al. identify disulfidptosis as a form of cell death resulting from aberrant accumulation of disulfide bonds in actin cytoskeleton proteins that is induced following glucose starvation and dependent on SLC7A11-mediated cystine uptake.

How cargo proteins are selected for endosomal recycling by the Commander complex is unclear. Here the authors report that the cargo adaptor SNX17 interacts with the Retriever sub-complex to facilitate cargo entry into the Commander endosomal recycling pathway and show that cargo relieves an autoinhibited conformation of SNX17 to promote SNX17-Commander coupling.

HPS is a rare autosomal recessive disorder that cause dysfunctions of the lungs, intestine, kidneys, and heart. Here, the authors report the structure of the BLOC complex, BLOC-3 and provides a framework to understand how BLOC-3 cooperates with Rab GTPases (RAB32/38 and RAB9A) to regulate the biogenesis of lysosome-related organelles.

Recycling of proteins that have entered the endosome is essential to homeostasis. The COMMD/CCDC22/CCDC93 (CCC) complex is regulator of recycling but the molecular mechanisms are unclear. Here, the authors report that the CCC complex regulates endosomal recycling by maintaining PI3P levels on endosomal membranes.

Endosomal recycling relies on SNX17 to transport membrane proteins via Retriever. Here, authors reveal the mechanisms of SNX17 autoinhibition and its interaction with Retriever, uncovering a broader family of factors with similar binding strategies.

Different environmental stressors induce different subtypes of stress granules (SGs), and each of them presumably have distinct functions. Here the authors provide a framework for understanding the compositional and functional heterogeneity of SGs, and see that TRIM25 mainly associates with anti-viral SGs.

Rag-GTPases play roles in sensing nutrient availability, and it is not fully known how they contribute to energy-consuming immunological processes such as the B cell response. Here authors show that genomic deletion fo RagA/RagB distrupts both T-dependent and T-independent humoral immune responses, independent of mechanistic target of rapamycin complex 1 but involving the transcription factors TFEB and TFE3.

Retromer is recruited to endosomes by the small GTPase Rab7 and sorting nexin 3. Here, the authors report the interaction between a GTPase-activating protein TBC1d5 and Rab7, examine the biochemical details of the interaction with retromer, and discuss the implications for receptor trafficking.

A model accounting for the properties of the local chromatin environment predicts the modulation of patterns in gene expression and helps screen for chemotherapeutic adjuvants that lead to an enhanced therapeutic response in cancer cells.

Neutrophils can respond to many chemotactic signals, but how these cells 'prioritize' such signals to react to invading pathogens has remained unclear. The phosphatase PTEN seems to be critical in directing the migration of neutrophils toward their end target in a complex milieu of competing signals.

Responsive exocytosis in neutrophil leukocytes involves actin depolymerisation-dependent sequential release of gelatinase granules, then strongly pro-inflammatory azurophilic granules. Here authors show that the actin nucleator protein WASH facilitates the initial step of innate immune activation by gelatinase granules while inhibiting release of pro-inflammatory granules.

The study presents a high-resolution structure of the retriever complex and a model of the retriever–CCC assembly, providing a mechanistic framework for studying how retriever facilitates endosomal recycling of diverse membrane proteins.

The T-cell cytoskeleton is a complex intracellular network of structural, adaptor and signalling molecules. This Review discusses recent advances in our understanding of its role in the initiation and maintenance of T-cell activation during antigen-presenting-cell recognition.

The regulation and coordination of F-actin networks are not well understood. Here, the authors show an antagonistic relationship between endosomal F-actin assembly and cortical bundle integrity during epithelial tube maturation that is regulated by kinase and phosphatase activity modifying WASH.

Low density lipoprotein receptor (LDLR) is crucial for cholesterol homeostasis. Here, the authors show that components of the CCC-protein complex, CCDC22 and COMMD1, facilitate the endosomal sorting of LDLR and that mutations in these genes cause hypercholesterolemia in dogs and mice, providing new insights into regulation of cholesterol homeostasis.

In cells, WAVE protein, a central regulator of actin dynamics during cell motility, is constitutively incorporated into WAVE regulatory complex (WRC), is normally present in an inactive state and can be activated by a number of inputs. These authors present the structure and mechanistic analysis of WRC. The combined data reveal how the WAVE protein is inhibited within the WRC complex and provide mechanisms for WRC activation at the plasma membrane.

McNally et al. identify the retriever complex as required for endosomal cargo recycling. Retriever binds SNX17, the CCC and WASH complexes to govern cell surface expression of integrins, receptors and transporters.