
Different colon cancer cell lines display distinct degrees of asymmetry in the partitioning of cytoplasmic components during cell division, which can be accurately quantified using a combination of flow cytometry measurements and theoretical modeling.


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quantifying-asymmetric-cell-division-in-colon-cancer-through-flow-cytometry-and-microscopy


Quantifying Asymmetric Cell Division in Colon Cancer through Flow Cytometry and Microscopy


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Heterotrimeric G proteins are less abundant on endocytic vesicles compared to the plasma membrane, suggesting inefficient loading of G proteins onto internalized membranes.


Classical G protein-coupled receptor (GPCR) signaling takes place in response to extracellular stimuli and involves receptors and heterotrimeric G proteins located at the plasma membrane. It has recently been established that GPCR signaling can also take place from intracellular membrane compartments, including endosomes that contain internalized receptors and ligands. While the mechanisms of GPCR endocytosis are well understood, it is not clear how well internalized receptors are supplied with G proteins. To address this gap we use gene editing, confocal microscopy, and bioluminescence resonance energy transfer to study the distribution and trafficking of endogenous G proteins. We show here that constitutive endocytosis is sufficient to supply newly internalized endocytic vesicles with 20-30% of the G protein density found at the plasma membrane. We find that G proteins are present on early, late, and recycling endosomes, are abundant on lysosomes, but are virtually undetectable on the endoplasmic reticulum, mitochondria, and the medial Golgi apparatus. Receptor activation does not change heterotrimer abundance on endosomes. Our findings provide a subcellular map of endogenous G protein distribution, suggest that G proteins may be partially excluded from nascent endocytic vesicles, and are likely to have implications for GPCR signaling from endosomes and other intracellular compartments.

### Competing Interest Statement

The authors have declared no competing interest.

Visualization of endogenous G proteins on endosomes and other organelles

inefficient-endocytosis-limits-heterotrimeric-g-protein-abundance-on-endosomes


Inefficient Endocytosis Limits Heterotrimeric G Protein Abundance on Endosomes



Upd2, a cytokine produced by the Drosophila fat body, is essential for maintaining the disciplined, directional migration of tracheal stem cells through the activation of the JAK/STAT signaling pathway and the regulation of planar cell polarity genes.


Coordinated activation and directional migration of adult stem cells are essential for maintaining tissue homeostasis. Drosophila tracheal progenitors are adult stem cells that migrate posteriorly along the dorsal trunk to replenish degenerating branches that disperse the FGF mitogen. However, it is currently unknown how the overall anterior-to-posterior directionality of such migration is controlled. Here we show that individual progenitor cells migrate together in a concerted, disciplined manner, a behavior that is dependent on the neighboring fat body. We identify the fat body-derived cytokine, Upd2, in targeting and inducing JAK/STAT signaling in tracheal progenitors to maintain their directional migration. Perturbation of either Upd2 production in fat body or JAK/STAT signaling in trachea causes aberrant bidirectional migration of tracheal progenitors. We show that JAK/STAT signaling promotes the expression of genes involved in planar cell polarity leading to asymmetric localization of Fat in progenitor cells. We provide evidence that Upd2 transport requires Rab5- and Rab7-mediated endocytic sorting and Lbm-dependent vesicle trafficking. Our study thus uncovers an inter-organ communication in the control of disciplined migration of tracheal progenitor cells, a process that requires vesicular trafficking of fat body-derived cytokine Upd2 and JAK/STAT signaling-mediated activation of PCP genes.

### Competing Interest Statement

The authors have declared no competing interest.

Fat body-derived cytokine Upd2 controls disciplined migration of tracheal stem cells in Drosophila

fat-body-derived-cytokine-upd2-regulates-the-directional-migration-of-tracheal-stem-cells-in-drosophila


Fat Body-Derived Cytokine Upd2 Regulates the Directional Migration of Tracheal Stem Cells in Drosophila



The helical actin structure in the sperm midpiece undergoes a reorganization at the time of sperm-egg fusion, which triggers a decrease in midpiece diameter and motility arrest, both of which are required to complete the fusion process during fertilization.


Mammalian sperm delve into the female reproductive tract to fertilize the female gamete. The available information about how sperm regulate their motility during the final journey to the fertilization site is extremely limited. In this work, we investigated the structural and functional changes in the sperm flagellum after AE and during the interaction with the eggs. The evidence demonstrates that the double helix actin network surrounding the mitochondrial sheath of the midpiece undergoes structural changes prior to the motility cessation. This structural modification is accompanied by a decrease in diameter of the midpiece and is driven by intracellular calcium changes that occur concomitant with a reorganization of the actin helicoidal cortex. Midpiece contraction occurs in a subset of cells that undergo AE, live-cell imaging during in vitro fertilization showed that the midpiece contraction is required for motility cessation after fusion is initiated. These findings provide the first evidence of the F-actin network’s role in regulating sperm motility, adapting its function to meet specific cellular requirements during fertilization, and highlighting the broader significance of understanding sperm motility.

Significant statement In this work, we demonstrate that the helical structure of polymerized actin in the flagellum undergoes a rearrangement at the time of sperm-egg fusion. This process is driven by intracellular calcium and promotes a decrease in the sperm midpiece diameter as well as the arrest in motility, which is observed after the fusion process is initiated.

### Competing Interest Statement

The authors have declared no competing interest.

Reorganization of the Flagellum Scaffolding Induces a Sperm Standstill During Fertilization

structural-reorganization-of-the-sperm-flagellum-facilitates-fertilization-by-inducing-motility-cessation


Structural Reorganization of the Sperm Flagellum Facilitates Fertilization by Inducing Motility Cessation



PP2A-B56 단백질 인산분해효소 복합체가 Mid1 단백질 수준을 조절하여 효모 세포분열을 적절하게 유도한다.


Protein phosphorylation regulates many steps in the cell division process including cytokinesis. In the fission yeast S. pombe , the anillin-like protein Mid1 sets the cell division plane and is regulated by phosphorylation. Multiple protein kinases act on Mid1, but no protein phosphatases have been shown to regulate Mid1. Here, we discovered that the conserved protein phosphatase PP2A-B56 is required for proper cytokinesis by promoting Mid1 protein levels. We find that par1 Δ cells lacking the primary B56 subunit divide asymmetrically due to the assembly of misplaced cytokinetic rings that slide toward cell tips. These par1 Δ mutants have reduced whole-cell levels of Mid1 protein, leading to reduced Mid1 at the cytokinetic ring. Restoring proper Mid1 expression suppresses par1 Δ cytokinesis defects. This work identifies a new PP2A-B56 pathway regulating cytokinesis through Mid1, with implications for control of cytokinesis in other organisms.

### Competing Interest Statement

The authors have declared no competing interest.

PP2A-B56 regulates Mid1 protein levels for proper cytokinesis in fission yeast

pp2a-b56-조절-단백질-mid1의-수준을-조절하여-분열효모의-적절한-세포분열을-유도한다


PP2A-B56 조절 단백질 Mid1의 수준을 조절하여 분열효모의 적절한 세포분열을 유도한다



Lysosomes selectively remove damaged sections of the mitochondrial inner membrane through a microautophagy-like process that forms vesicles derived from the inner mitochondrial membrane, thereby protecting the organelle from localized injury.


We show that cytosolic inner mitochondrial membrane vesicles, devoid of outer mitochondrial membrane or mitochondrial matrix, are formed during resting state and directly herniate into lysosomes through pores formed by voltage-dependent anion channel 1 in the outer mitochondrial membrane, thereby allowing their selective removal.

Lysosomes drive the piecemeal removal of mitochondrial inner membrane - Nature

lysosomes-selectively-remove-damaged-sections-of-mitochondrial-inner-membrane-through-vesicle-formation


Lysosomes Selectively Remove Damaged Sections of Mitochondrial Inner Membrane through Vesicle Formation



Caveolae act as a dynamic membrane reservoir that senses and responds to changes in membrane tension, coupling this to the regulation of actomyosin contractility and cell migration.


Caveolae play fundamental roles in mechanotransduction. Critical to caveolae function is their ability to flatten out in response to an increase in membrane tension, thereby acting as a membrane reservoir to buffer acute mechanical stress. Cycles of caveolae assembly and disassembly also regulate membrane tension at the rear of migrating cells via RhoA/ROCK-mediated actomyosin contractility. However, the molecular mechanisms that couple caveolae-mediated mechanotransduction to cortical actin dynamics are poorly understood. Here we used biotin-based proximity labelling and quantitative mass spectrometry to define a caveolae-associated interactome in migrating RPE1 cells at steady state and in response to an acute increase in membrane tension induced by hypo-osmotic shock. Our data reveal a dynamic caveolae-associated protein network composed of focal adhesion proteins and cortical actin regulators that is highly sensitive to changes in membrane tension. We show that membrane tension differentially controls the association of ROCK and the RhoGAP ARHGAP29 with caveolae and that ARHGAP29 regulates caveolin-1 Y14 phosphorylation, caveolae rear localisation and RPE1 cell migration. Caveolae in turn regulate ARHGAP29 expression, most likely through the control of YAP signalling. Taken together, our work uncovers a membrane tension-dependent functional coupling between caveolae and the rear-localised actin cytoskeleton, which provides a framework for dissecting the molecular mechanisms underlying caveolae-regulated mechanotransduction pathways.

### Competing Interest Statement

The authors have declared no competing interest.

Time-resolved proximity proteomics uncovers a membrane tension-sensitive caveolin-1 interactome at the rear of migrating cells

rapid-disassembly-and-reassembly-of-caveolae-in-response-to-changes-in-membrane-tension-regulates-cell-migration


Rapid Disassembly and Reassembly of Caveolae in Response to Changes in Membrane Tension Regulates Cell Migration



蛋白質ドロップレットの濡れ性が細胞間の密着結合の形成に重要な役割を果たしている。


Step-by-step formation of tight junctions between epithelial cells.

Protein droplets spread to seal tight junctions

細胞間の密着結合形成における蛋白質ドロップレットの役割


Protein condensates formed through liquid-liquid phase separation can wet and remodel cell membranes, facilitating the formation of specialized tight junctions between cells.


protein-droplets-facilitate-the-formation-of-tight-junctions-between-cells


Protein Droplets Facilitate the Formation of Tight Junctions Between Cells



Chaperone complexes from the ER and cytosol, specifically DNAJB12 and DNAJB14, regulate the reflux of ER proteins to the cytosol, which inhibits the activity of wild-type p53 in cancer cells.


The Endoplasmic Reticulum (ER) is an essential sensing organelle responsible for the folding and secretion of almost one-third of eukaryotic cells’ total proteins. The ER contains numerous enzymes and chaperones which assist in oxidative protein folding and other posttranslational modifications. However, environmental, chemical, and genetic insults often lead to protein misfolding in the ER, accumulating misfolded proteins, altering homeostasis, and causing ER stress. Recently, we reported a novel ER surveillance mechanism by which proteins from the secretory pathway are refluxed to the cytosol to relieve the ER of its content during stress. In cancer cells, the refluxed proteins gain new pro-survival functions, thereby increasing cancer cell fitness. We termed this phenomenon ER to CYtosol Signaling (or “ ERCY”) . In yeast, ERCYS is regulated by HLJ1 (an ER-resident tail-anchored HSP40 cochaperone). Here, we found that in mammalian cells, HLJ1 has five putative orthologs possessing J-domains facing the cytosol. Among those, DNAJB12 and DNAJB14 appear to be the most significant. Mechanistically, we found that DNAJB12 and DNAJB14 bind the cytosolic HSC70 and its cochaperone – SGTA - through their cytosolically localized J-domains to facilitate ER-protein reflux to the cytosol. Moreover, we found that DNAJB12 is necessary and sufficient to drive this phenomenon to increase AGR2 reflux and inhibit wt-p53 during ER stress. Thus, we concluded that targeting the DNAJB12/14-HSC70/SGTA axis is a promising strategy to inhibit ERCYS and impair cancer cell fitness.

### Competing Interest Statement

The authors have declared no competing interest.

Chaperone Complexes From The Endoplasmic Reticulum (ER) And The Cytosol Inhibit wt-p53 By Activation The ER To Cytosol Signaling

chaperone-complexes-from-the-endoplasmic-reticulum-er-and-the-cytosol-inhibit-wild-type-p53-by-activating-the-er-to-cytosol-signaling-pathway


Chaperone Complexes from the Endoplasmic Reticulum (ER) and the Cytosol Inhibit Wild-Type p53 by Activating the ER-to-Cytosol Signaling Pathway
