ON THE COVER
A confocal image of HeLa cells in anaphase stained for NuMA (magenta) and RhoA (green). The chromosomes are stained with Hoechst 33342 (cyan). NuMA and RhoA signal is present in a mutually exclusive manner at the cell membrane. This compartmentalized localization of NuMA and RhoA is critical for coordinating chromosome segregation with cleavage furrow formation. Image © Sana et al., 2022 https://doi.org/10.1083/jcb.202203127
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People & Ideas
Sachihiro Matsunaga: FISHing the nuclear architecture of plant cells
Sachihiro Matsunaga studies the nuclear structure and chromatin dynamics of plants.
A plant-specific bridging adaptor for amphisome biogenesis
Koestel and Batoko preview work from the Kang and Dagdas labs that reveals the existence of amphisome compartments in plant cells and identifies CFS1 as a bridging adaptor for amphisome formation.
Letting go: Dishevelled phase separation recruits Axin to stabilize β-catenin
Babcock and Pruitt preview work from Kang et al. describing how LLPS of Dishevelled promotes assembly of Wnt signalosome condensates while also disrupting the β-catenin destruction complex.
Temporal and spatial metabolite dynamics impart control in adipogenesis
Kristin Eckel-Mahan previews work from Sánchez-Ramírez and Ung et al. that elucidates how NAD+ metabolism modulates the early stages of adipogenic differentiation whereas SIRT1’s effects are limited to terminal stages.
ER–endosome contacts master the ins and outs of secretory endosomes
Eva Marie Wenzel and Camila Raiborg highlight work from Verweij and colleagues which examines the mechanisms by which ER–endosome contact sites modulate exosome maturation and secretion.
MR1: An unconventional twist in the tail
MR1 is a conserved molecule that binds microbial vitamin B metabolites and presents them to unconventional T cells. Lim and colleagues uncover the role of AP2 in ensuring MR1 surface presentation, which relies on an atypical motif within the MR1 cytoplasmic tail.
mTORC1 beyond anabolic metabolism: Regulation of cell death
Zhu et al. review the current knowledge on how mTORC1 activity is connected to cell death regulation through metabolic and signaling pathways.
Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation
Mitochondrial protein mitoguardin-2, at contacts with the ER or with lipid droplets (LDs), binds fatty acids and phospholipids, and non-specifically transfers phospholipids between membranes in vitro. Its lipid transfer ability is required for roles in mitochondrial and LD biology.
Dishevelled phase separation promotes Wnt signalosome assembly and destruction complex disassembly
Kang et al. demonstrate that Dvl2 undergoes phase separation and displays a rapid accumulation to the plasma membrane upon Wnt stimulation. Dvl2 phase separation plays a crucial role in assembly of the Wnt receptor signalosome and disruption of the β-catenin destruction complex.
Nucleoplasmic lamin C rapidly accumulates at sites of nuclear envelope rupture with BAF and cGAS
Kono et al. show the rapid recruitment of nucleoplasmic lamin C to sites of nuclear envelope rupture with barrier-to-autointegration factor (BAF). Lamin A/C is also involved in nuclear BAF accumulation and cytoplasmic cGAS association with chromatin at the rupture sites.
The central scaffold protein CEP350 coordinates centriole length, stability, and maturation
Karasu et al. aim to shed light on mechanisms of how the length and structural integrity of centrioles, which are stable microtubule-based structures, are ensured. They show that the centriolar protein CEP350 regulates length, stability, and maturation of centrioles and identify CEP350 as guardian of centriole integrity.
Nuclear tension controls mitotic entry by regulating cyclin B1 nuclear translocation
Mitotic entry is regulated by the activity of cyclin B1-CDK1 complexes. In this study, Dantas et al. show that actomyosin-dependent nuclear tension during prophase regulates cyclin B1 nuclear translocation and has implications for chromosome segregation efficiency.
Membrane compartmentalization of Ect2/Cyk4/Mklp1 and NuMA/dynein regulates cleavage furrow formation
Chromosome separation is coupled with cleavage furrow formation during anaphase. Sana, Rajeevan, et al. demonstrate that the mutually exclusive localization of NuMA and Ect2/Cyk4/Mklp1 ensures dynein/dynactin and RhoA at distinct membrane zones to coordinate chromosome separation with cleavage furrow formation.
Coordinated metabolic transitions and gene expression by NAD+ during adipogenesis
Sánchez-Ramirez, Ung et al. show that NAD+ bioavailability controls adipogenic differentiation obstructing adipocyte commitment, downregulating ribosomal proteins–coding genes and leading to quiescent metabolic state. Instead, the NAD+-dependent SIRT1 deacetylase is essential for terminal differentiation of pre-adipocytes and regulates subcellular compartmentalization of redox metabolism during adipogenesis.
ER membrane contact sites support endosomal small GTPase conversion for exosome secretion
Exosomes are derived from endosomal compartments with an ill-defined molecular identity and whose trafficking steps to secretion are poorly understood. Using advanced imaging approaches, the authors identified these compartments as pre-lysosomal endosomes that require dynamic membrane contact sites with the endoplasmic reticulum to induce a prosecretory cascade of small-GTPases.
Liquid–liquid phase separation facilitates the biogenesis of secretory storage granules
The biogenesis of secretory granules (SGs) is poorly understood. Here, we show that chromogranin proteins form a liquid scaffold upon entry into the milieu of the trans-Golgi network (TGN). These scaffolds recruit clients such as proinsulin and facilitate their transport to SGs.
Gradient tracking in mating yeast depends on Bud1 inactivation and actin-independent vesicle delivery
To sense potential mating partners’ positions, yeast uses a default polarity site to assemble a gradient tracking machine (GTM), which redistributes up the pheromone gradient. Here, Wang et al. show that GTM redistribution requires default-site inactivation and actin-independent vesicle delivery.
TBC1D18 is a Rab5-GAP that coordinates endosome maturation together with Mon1
Hiragi et al. identify TBC1D18 as a Rab5-GAP that is associated with Mon1 and mediates endosome maturation. They propose a new endosome maturation model in which Mon1–Ccz1 together with TBC1D18 coordinates endosome maturation by inactivating Rab5 and activating Rab7.
Plant autophagosomes mature into amphisomes prior to their delivery to the central vacuole
Zhao et al. reveal amphisome compartments in plant cells. By characterizing the autophagy adaptor CFS1 that can interact with both ATG8, and the ESCRT-I complex subunit VPS23A; they show that autophagosomes are sorted at amphisomes before arriving their final destination, the central vacuole.
WDR91 specifies the endosomal retrieval subdomain for retromer-dependent recycling
Liu et al. identify WDR91 as an important player in retromer-dependent recycling. WDR91 promotes the interaction of Rab7 with SNX-retromer components and interacts with FAM21, facilitating the formation of the endosomal retrieval subdomain.
V. cholerae MakA is a cholesterol-binding pore-forming toxin that induces non-canonical autophagy
Jia et al. identify cholesterol as the primary lipid responsible for interaction between Vibrio cholerae toxin MakA and host membranes. They further characterize a sophisticated mechanism of recurrent membrane damage regulated by pH-dependent pore formation, leading to V-ATPase-dependent unconventional LC3 lipidation on damaged endolysosomal membranes.
Aberrant phosphorylation inactivates Numb in breast cancer causing expansion of the stem cell pool
Filippone et al. show that the frequent activation of PKCs leads to aberrant phosphorylation of the tumor suppressor Numb in breast cancer. Aberrantly phosphorylated Numb fails to determine asymmetric cell division, resulting in expansion of the cancer stem cell compartment, associated with an aggressive disease course.
Regulation of Cdc42 protein turnover modulates the filamentous growth MAPK pathway
González and Cullen demonstrate that the Rho GTPase Cdc42 is degraded by a NEDD4 ubiquitin ligase and HSP40 and HSP70 proteins to regulate the activity of the protein. Moreover, a Cdc42p-interacting protein prevents its degradation to control the filamentous growth MAPK pathway.
Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells
Weier et al. demonstrate that dendritic cell maturation upon antigen encounter leads to a modified cell division cycle accompanied by accumulation and untimely duplication of centrioles. Extra centrosomes act as functional microtubule-organizing centers, which promote immune cells’ effector functions such as directional locomotion, cytokine secretion, and T cell activation.
Integrin-based adhesion compartmentalizes ALK3 of the BMPRII to control cell adhesion and migration
Decoupling of the functions between ALK3 and BMPRII: ALK3 segregation in focal adhesion is BMP2 dependent and BMPRII independent to control cell adhesion processes and SMAD stability.
A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells
Lim et al. investigate the internalization mechanism of the antigen presenting molecule, MR1. Recognition of a conserved atypical motif in MR1’s cytoplasmic tail by AP2 defines the endocytosis rate and duration of MR1–metabolite cell surface display, functioning as the “off” switch for MR1 presentation.