Biology subjects

Kubota, Y.

Publications and source records attributed to Kubota, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Stromal CTHRC1 protects the valvular interstitium from macrophage-associated inflammatory remodeling and calcification

Background: Calcific aortic valve disease (CAVD) is characterized by progressive inflammatory and fibrocalcific remodeling. Although valvular interstitial cells (VICs) are generally considered to drive fibrosis and osteogenic remodeling, whether injury-activated VICs mount endogenous protective responses that preserve the valvular interstitial microenvironment and restrain calcification remains unknown. Methods: We performed spatial transcriptomic profiling of aortic valves in a mouse model of endothelial injury-induced CAVD to define early injury-responsive programs within the valvular interstitium. The cellular origin and spatial distribution of candidate protective factors were examined by immunohistochemistry and lineage tracing, and their relevance to human disease was assessed using stenotic aortic valves. The functional role of CTHRC1 was investigated using genetic Cthrc1 deficiency combined with longitudinal hemodynamic assessment, histological analysis, and spatial transcriptomic profiling. Results: Spatial transcriptomics identified Cthrc1 as a prominent component of an early injury-induced stromal response in the expanding valvular interstitium. CTHRC1 was strongly expressed in activated VICs within thickened murine valve leaflets and human stenotic aortic valves. Lineage tracing demonstrated that the expanded VIC population arose predominantly from PDGFR{beta}+ resident interstitial cells, with minimal endothelial contribution. Despite comparable early hemodynamic responses to endothelial injury, Cthrc1 deficiency exacerbated chronic valvular calcification. Spatial profiling of Cthrc1-deficient valves revealed pronounced interstitial accumulation of galectin-3+ foamy macrophages, accompanied by mitochondrial respiratory-chain signature loss and cell death-associated pathway activation. These findings indicate that transient CTHRC1 induction after endothelial injury defines an endogenous stromal protective response that preserves the valvular interstitial microenvironment and limits macrophage-associated tissue injury and subsequent dystrophic calcification. Conclusions: Injury-activated VICs are not merely effectors of pathological remodeling, but can engage an endogenous tissue-protective response through CTHRC1. These findings identify a previously unrecognized stromal defense mechanism linking endothelial injury to macrophage-associated inflammatory remodeling and dystrophic calcification and suggest CTHRC1-dependent stromal protection as a potential therapeutic axis for limiting CAVD progression.

molecular biology↗

bioRxiv2026

Meso2EM: a cross-scale CLEM workflow linking mesoscale functional imaging to targeted electron microscopy

Meso2EM is a correlative light and electron microscopy workflow that transfers neurons selected from mesoscale functional images to targeted electron microscopy. We recorded Ca{superscript 2} signals from layer 2/3 neurons across a contiguous 3 x 3 mm cortical field in awake mice and reidentified a selected neuron after fixation and tangential sectioning. Lectin-labeled vascular architecture served as a shared landmark across in vivo two-photon imaging, confocal microscopy, laboratory micro-CT of resin-embedded tissue, and block-surface scanning electron microscopy, guiding focused-ion-beam scanning electron microscopy to the target cell body. The same progressive-targeting principle also supported serial ATUM-SEM reconstruction of an in vivo-tracked dendrite and serial transmission electron microscopy of optically selected dendrites from a patch-clamp-recorded Martinotti cell. Meso2EM therefore provides a practical route for preserving target identity across large changes in scale and specimen state while restricting electron-microscopy acquisition to a selected region.

neuroscience↗

bioRxiv2026

Adrenal Gland Macrophage-derived TGF-β Governs Vascular Permeability to Drive Monocyte Recruitment during Stress

The adrenal glands are central regulators of systemic stress responses through tightly controlled glucocorticoid production. Yet, the contribution of local immune-vascular interactions to adrenal stress adaptation remains poorly understood. Here, we investigated the role of adrenal gland macrophages in coordinating stress-induced immune remodeling and vascular function. By integrating single-cell RNA sequencing datasets across four distinct stress models, including acute cold exposure, chronic social defeat, chronic inflammation, and systemic Candida albicans infection, we identified a conserved increase in monocyte recruitment to the adrenal gland, accompanied by dynamic macrophage transitions. Comparative transcriptomic and ligand-receptor analyses identified transforming growth factor-{beta} (TGF{beta}) as a dominant macrophage-derived signal targeting adrenal endothelial cells across all stress conditions. Pharmacological blockade of TGF{beta} receptor signaling reduced endothelial activation, vascular permeability, and monocyte infiltration into the adrenal gland following stress, without directly altering resident macrophage numbers. Using genetic fate-mapping and conditional knockout models, we demonstrate that macrophage-derived, but not endothelial-derived, TGF{beta} is required to promote enhanced endothelial adhesion molecule expression, vascular fenestration, permeability, and efficient monocyte recruitment. Loss of macrophage TGF{beta} production also led to exacerbated systemic stress hormone levels. Together, these findings uncover a previously unrecognized macrophage-endothelial axis in the adrenal gland, whereby macrophage-derived TGF{beta} regulates vascular properties to support immune cell recruitment and stress adaptation. This immune-vascular crosstalk provides new mechanistic insights into adrenal homeostasis and suggests potential therapeutic avenues for disorders associated with dysregulated chronic stress.

immunology↗

bioRxiv2026

The REFLEX system enables in vivo identification of perivascular angiogenic macrophages in the heart

Direct identification of physically interacting cells in vivo remains challenging because conventional interactome analyses infer signaling partners from transcriptomes and cannot reveal which cells are in direct contact. In pressure-overload induced cardiac remodeling, VEGF-A plays a central role in the maintenance of vascular integrity and cardiac function. However, the cell type which produces VEGF-A and how the VEGF-A peptide is delivered to vascular endothelial cells remains unclear. Here, we developed a genetically encoded platform that combines REFLEX mice with HUNTERuni-seq, enabling unbiased detection and transcriptional profiling of the cells that physically interact with vascular endothelial cells. The REFLEX and HUNTERuni-seq approach identified subpopulations of Vegfa positive macrophages which we named perivascular angiogenic macrophages (PVAMs). Although the amount of VEGF-A in PVAMs is small, loss of VEGF-A in PVAMs impaired angiogenesis and systolic function during pressure overload. We additionally show that direct contact between PVAMs and endothelial cells is critical for the delivery of VEGF-A to endothelial cells. Conventional interactome analysis predicted that cardiomyocytes as dominant sources of VEGF-A in the heart. However, cardiomyocyte Vegfa deletion had no effect on capillary density nor systolic function in a model of heart failure. These results suggest that VEGF-A signaling does not rely on free diffusion through the interstitium and that cellular proximity and physical contact between PVAMs and endothelial cells are the key determinants of effective signal delivery. Together, these findings establish REFLEX and HUNTERuni-seq as a versatile platform for uncovering biologically critical cell-to-cell interactions and provide new insight into intercellular communication in pathological tissue contexts.

cell biology↗

bioRxiv2025

Artificial hibernation uncovers distinct synaptic engram architecture for memory retention

The memory trace at the neuronal and synaptic levels remains controversial. Stable, larger spines are thought to support memory, but the high turnover of dendritic spines and the drifting of neuronal representations following memory formation suggest alternative possibilities. To elucidate a structural trace underlying memory retention, we utilize a mouse model of artificial hibernation. During hibernation, hippocampal neurons exhibited a substantial reduction in their activity and an extensive elimination of dendritic spines and synapses. Despite these changes, their memory and associated hippocampal neuronal representations are intact after arousal. We find that a subset of spines is maintained during hibernation. These spatially clustered engram-engram synapses are exclusively protected from elimination and characterized by synaptic contacts with multi-synaptic boutons. These findings suggest that synaptic engram architecture, rather than larger spines per se, is resilient to network remodeling and underlies long-term memory retention.

neuroscience↗

bioRxiv2025

The sympathoadrenal contribution to inferior vena cava formation

Vascular development is fundamental during embryogenesis. Although the molecular and cellular mechanisms of vascular formation have been extensively studied, the developmental basis common to anatomical variations in major veins remains poorly understood1-4. In particular, the renal segment of the inferior vena cava (IVC) exhibits marked anatomical variability, and these structural differences often affect the safety of retroperitoneal surgeries5,6. Here we show that the renal segment of the IVC in mouse embryos does not arise from the subcardinal vein (SubCV), as classically proposed7, but instead forms from a vascular plexus in the para-aortic ridge (PAR) closely associated with developing sympathetic and adrenal tissues. Three-dimensional imaging with molecular markers revealed the vascular plexus in PAR arises independently of the SubCV and develops in Zuckerkandl organ and adrenal gland primordia. Moreover, genetic models demonstrated that the development of the sympathetic and adrenal tissues contributes to the organization and remodeling of this vascular network. This sympathoadrenal contribution contrasts with the classical mesonephros-centric model and explains the consistent IVC structures observed even in the absence of renal development. Our findings suggest a mammal-specific mode of IVC formation driven by the emergence of dominant sympathetic paraganglia and reduced reliance on mesonephric filtration. This revised developmental framework provides insight into the evolutionary divergence of venous anatomy and may help interpret clinically significant vascular variations during abdominal surgery.

developmental biology↗

bioRxiv2025

Human-like monocular depth biases in deep neural networks

Human depth perception from 2D images is systematically distorted, yet the nature of these distortions is not fully understood. To gain insights into this fundamental problem, we compare human depth judgments with those of deep neural networks (DNNs), which have shown remarkable abilities in monocular depth estimation. Using a novel human-annotated dataset of natural indoor scenes and a systematic analysis of absolute depth judgments, we investigate error patterns in both humans and DNNs. Employing exponential-affine fitting, we decompose depth estimation errors into depth compression, per-image affine transformations (including scaling, shearing, and translation), and residual errors. Our analysis reveals that human depth judgments exhibit systematic and consistent biases, including depth compression, a vertical bias (perceiving objects in the lower visual field as closer), and consistent per-image affine distortions across participants. Intriguingly, we find that DNNs with higher accuracy partially recapitulate these human biases, demonstrating greater similarity in affine parameters and residual error patterns. This suggests that these seemingly suboptimal human biases may reflect efficient, ecologically adapted strategies for depth inference from inherently ambiguous monocular images. However, while DNNs capture metric-level residual error patterns similar to humans, they fail to reproduce human-level accuracy in ordinal depth perception within the affine-invariant space. These findings underscore the importance of evaluating error patterns beyond raw accuracy, providing new insights into how humans and computational models resolve depth ambiguity. Our dataset and methodology provide a framework for evaluating the alignment between computational models and human perceptual biases, thereby advancing our understanding of visual space representation and guiding the development of models that more faithfully capture human depth perception. Author summaryUnderstanding the characteristics of errors in depth judgments exhibited by humans and deep neural networks (DNNs) provides a foundation for developing functional models of human brain and artificial models with enhanced interpretability. To address this, we constructed a human depth judgment dataset using indoor photographs and compared human depth judgments with those of DNNs. Our results show that humans systematically compress far distances and exhibit distortions related to viewpoint shift, which remain remarkably consistent across observers. Strikingly, the better the DNNs were at depth estimation, the more they also exhibited human-like biases. This suggests that these seemingly suboptimal human biases could in fact reflect efficient strategies for inferring 3D structure from ambiguous 2D inputs. However, we also found a limit: while DNNs mimicked some human errors, they werent as good as humans at judging the relative order of objects in depth, especially when we accounted for viewpoint distortions. We believe that our dataset and discovery of multiple error factors will drive further comparative studies between humans and DNNs, facilitating model evaluations that go beyond simple accuracy to uncover how depth perception truly works--and how it might best be replicated in computational models.

neuroscience↗

bioRxiv2024

Embryological cellular origins and hypoxia-mediated mechanisms in PIK3CA-Driven refractory vascular malformations

Congenital vascular malformations, affecting 0.5% of the population, often occur in the head and neck, complicating treatment due to the critical functions in these regions. Our previous research identified distinct developmental origins for blood and lymphatic vessels in these areas, tracing them to the cardiopharyngeal mesoderm (CPM), which contributes to the development of the head, neck, and cardiovascular system in both mouse and human embryos. In this study, we investigated the pathogenesis of these malformations by expressing Pik3caH1047R in the CPM. Mice expressing Pik3caH1047R in the CPM developed vascular abnormalities restricted to the head and neck. Single-cell RNA sequencing revealed that Pik3caH1047R upregulates Vegf-a expression in endothelial cells through HIF-mediated hypoxia signaling. Human samples supported these findings, showing elevated HIF-1 and VEGF-A in malformed vessels. Notably, inhibition of HIF-1 and VEGF-A in the mouse model significantly reduced abnormal vasculature. These results highlight the role of embryonic origins and hypoxia-driven mechanisms in vascular malformations, providing a foundation for the development of therapies targeting these difficult-to-treat conditions.

molecular biology↗

bioRxiv2024

ENDOTHELIAL PROX1 INDUCES BLOOD-BRAIN BARRIER DISRUPTION IN THE CENTRAL NERVOUS SYSTEM

The central nervous system (CNS) parenchyma has conventionally been believed to lack lymphatic vasculature, likely due to a non-permissive microenvironment that hinders the formation and growth of lymphatic endothelial cells (LECs). Recent findings of ectopic expression of LEC markers including Prospero Homeobox 1 (PROX1), a master regulator of lymphatic differentiation, and the vascular permeability marker Plasmalemma Vesicle Associated Protein (PLVAP), in certain glioblastoma and brain arteriovenous malformations (AVMs), has prompted investigation into their roles in cerebrovascular malformations, tumor environments, and blood-brain barrier (BBB) abnormalities. To explore the relationship between ectopic LEC properties and BBB disruption, we utilized endothelial cell-specific Prox1 overexpression mutants. When induced during embryonic stages of BBB formation, endothelial Prox1 expression induces hybrid blood-lymphatic phenotypes in the developing CNS vasculature. This effect is not observed when Prox1 is overexpressed during postnatal BBB maturation. Ectopic Prox1 expression leads to significant vascular malformations and enhanced vascular leakage, resulting in BBB disruption when induced during both embryonic and postnatal stages. Mechanistically, PROX1 downregulates critical BBB-associated genes, including {beta}-catenin and Claudin-5, which are essential for BBB development and maintenance. These findings suggest that PROX1 compromises BBB integrity by negatively regulating BBB-associated gene expression and Wnt/{beta}-catenin signaling.

developmental biology↗

bioRxiv2023

Nuclear membrane protein Bqt4 maintains nuclear envelope integrity by recruiting phosphatidic acid

The nuclear envelope (NE) is a permeable barrier that maintains nuclear-cytoplasmic compartmentalization and ensures nuclear function; however, it ruptures in various situations such as mechanical stress and mitosis. Although the protein components for sealing a ruptured NE have been identified, the mechanism by which lipid components are involved in this process remains to be elucidated. Here, we found that an inner nuclear membrane (INM) protein Bqt4 directly interacts with phosphatidic acid (PA) and serves as a platform for NE maintenance in the fission yeast Schizosaccharomyces pombe. The intrinsically disordered region (IDR) of Bqt4, proximal to the transmembrane domain, binds to PA and forms a solid aggregate in vitro. Excessive accumulation of Bqt4 IDR in INM results in membrane overproliferation and lipid droplet formation in the nucleus, leading to centromere dissociation from the NE and chromosome missegregation. Our findings suggest that Bqt4 IDR controls nuclear membrane homeostasis by recruiting PA to the INM, thereby maintaining the structural integrity of the NE.

cell biology↗

bioRxiv2023

Rhythm Receptive Fields in Striatum of Mice Executing Complex Continuous Movement Sequences

By the use of a novel experimental system, the step-wheel, we investigated the neural underpinnings of complex and continuous movements. We recorded neural activities from the dorsolateral striatum and found neurons sensitive to movement rhythm parameters. These neurons responded to specific combinations of interval, phase, and repetition of movement, effectively forming what we term "rhythm receptive fields." Some neurons even responsive to the combination of movement phases of multiple body parts. In parallel, cortical recordings in sensorimotor areas highlighted a paucity of neurons responsive to multiple parameter combinations, relative to those in the striatum. These findings have implications for comprehending motor coordination deficits seen in brain disorders including Parkinsons disease. Movement encoding by rhythm receptive fields should streamline the brains capacity to encode temporal patterns, help to resolve the degrees of freedom problem. Such rhythm fields hint at the neural mechanisms governing effective motor control and processing of rhythmic information.

neuroscience↗

bioRxiv2023

Endothelial-fibroblast interactions during Scarb1 accelerate heart failure

Endothelial cells (ECs) maintain cardiac homeostasis and EC dysfunction causes heart failure progression. Moreover, pathological changes occur via interactions between multiple cells, including ECs. Here, we conducted single-cell RNA-seq analysis of non-cardiomyocytes in mouse hearts during heart failure progression to elucidate the pathological changes in ECs and fibroblasts (FBs) mediated by cell-cell interactions. We show that capillary and arterial ECs exhibit mesenchymal gene expression changes with heart failure progression, indicating that endothelial-to-mesenchymal transition (EndMT) is a major pathological alteration in ECs. We also found that the interaction between ECs and FBs was enriched during heart failure, particularly when involving Scavenger Receptor Class B Member 1 (Scarb1) in ECs. FBs induce mesenchymal gene alterations in ECs in the EC-FB co-culture system, which is inhibited by blocking SCARB1. RNA-seq analysis showed that administration of a SCARB1 inhibitor blocked mesenchymal gene expression, and inflammatory changes, suggesting that the EC-FB interaction via Scarb1 is important for EndMT induction in ECs. Systemic administration of a SCARB1 inhibitor attenuated heart failure progression and cardiac fibrosis. EC-specific Scarb1 knockout mouse showed improved cardiac function, suggesting a crucial role of Scarb1 in heart failure progression. Our results suggest that Scarb1 is a promising candidate for novel heart failure treatments that target ECs.

molecular biology↗

bioRxiv2023

Genetic and Geographic Patterns of Woody Plant Biosynthesis

BackgroundNatural products (NPs) are vital for promoting human health. Given the increasing threats of biodiversity loss and ecosystem degradation, understanding the geographical hotspots of NPs is essential to strategically prioritize areas for conservation, ensuring the sustained availability of these invaluable medicinal resources. MethodsWe constructed a global diversity map for 1,434 woody angiosperm species, each represented by existing genomic or transcriptomic data. We curated a list of 166 enzymes essential for the biosynthesis and structural diversity of NPs, and identified geographical hotspots of NPs by averaging enzyme presence across the grids. We also examined the distribution pattern of each enzyme. To gain deeper insights into NP distribution patterns, we performed a comparative analysis of enzyme groups responsible for the biosynthesis of two pharmacologically significant compounds with distinct biosynthetic pathways, shikonin derivatives and benzylisoquinoline alkaloids. FindingsOur study reveals a correlation between NP hotspots and biodiversity hotspots, with a subset of markers displaying unique, region-specific patterns. Comparative analysis of enzymes for shikonin derivatives and benzylisoquinoline alkaloids biosynthetic pathways shows similar pattern, with the former demonstrating a unique and region-specific distribution. InterpretationOur findings emphasize the importance of preserving biodiversity hotspots for sustaining NP-based medicinal resources. Additionally, the specific distribution of certain enzyme markers, such as those related to shikonin derivatives, suggests that some NPs may necessitate targeted conservation strategies. This study provides a foundational roadmap for identifying the geographical hotspots of NPs and developing targeted conservation strategies. FundingJapan Society for the Promotion of Science through the Grant-in-Aid for Scientific Research (A) 20H00651.

ecology↗

bioRxiv2023

Unique and shared functions of the Rad9-Hus1-Rad1 and Mre11-Rad50-Nbs1 complexes in ATR checkpoint activation and long-range DNA end resection in Xenopus egg extracts

Sensing and processing of DNA double-strand breaks (DSBs) are vital to genome stability. DSBs are primarily detected by the ATM checkpoint pathway, where the Mre11-Rad50-Nbs1 (MRN) complex serves as the DSB sensor. Subsequent DSB end resection promotes the transition from the ATM to the ATR checkpoint pathway, where replication protein A, MRN, and the Rad9-Hus1-Rad1 (9-1-1) checkpoint clamp serve as the DNA structure sensors. 9-1-1 and MRN recruit Topbp1, a critical checkpoint mediator that activates the ATR kinase. However, how multiple sensors contribute to regulating end resection and checkpoint activation remains ambiguous. Using DNA substrates that mimic extensively resected DSBs, we show here that MRN and 9-1-1 redundantly stimulate Dna2-dependent long-range end resection and ATR activation in Xenopus egg extracts. MRN serves as the loading platform for Dna2, ATM, and Topbp1. In contrast, 9-1-1 is dispensable for bulk Dna2 loading, and Topbp1 loading is interdependent with 9-1-1 in this pathway. ATR facilitates Mre11 phosphorylation and ATM dissociation. Our results delineate the molecular mechanism of and interplay between two redundant pathways that stimulate ATR checkpoint activation and long-range DSB end resection in vertebrates.

biochemistry↗

bioRxiv2023

Occurrence-based diversity estimation reveals macroecological and conservation knowledge gaps for global woody plants

Incomplete sampling of species geographic distributions has challenged biogeographers for many years to precisely quantify global-scale biodiversity patterns. After correcting for the spatial inequality of sample completeness, we generated a global species diversity map for woody angiosperms (82,974 species, 13,959,780 occurrence records). The estimated diversity demonstrated non-linear latitudinal and longitudinal patterns that were potentially related to region-specific biogeographic factors including current climate, paleoclimate, and topographical factors, while energy availability was the most important predictor at a global level. We identified the areas with potentially high species richness and rarity, but poorly explored, unprotected, and threatened by deforestation: they are distributed mostly at low latitudes across central South America, central Africa, subtropical China, and Indomalayan islands. These priority areas for botanical exploration would help to efficiently fill spatial knowledge gaps for better describing the status of biodiversity and improve the effectiveness of the protected area network for global woody plant conservation. TeaserBias-corrected diversity map based on occurrence records sheds new light on global macroecology and conservation of woody angiosperms.

ecology↗

bioRxiv2023

Ribosomal protein mutation suppresses gonadal leader cell migration defects in mig-17/ADAMTS mutants in Caenorhabditis elegans

The migration of the gonadal distal tip cells (DTCs) in Caenorhabditis elegans provides an excellent model for studying the migration of epithelial tubes during organogenesis. Mutations in the mig-17/ADAMTS gene cause misdirected migration of DTCs during gonad formation, resulting in deformed gonad arms. An amino-acid substitution in RPL- 20 corresponding to the mammalian RPL18a/eL20, a component of the 60S ribosomal large subunit, showed a slow growth phenotype and strongly suppressed the mig-17 gonadal defects. Slow-growing mutants clk-1 and clk-2 also suppressed mig-17, although weaker than rlp-20 mutants. MIG-17 recruits FBL-1C/fibulin-1C to the gonadal basement membrane to regulate DTC migration. Reducing the gene dosage of fbl-1 by half partially compromised the suppressor activity of the mutant rpl-20 gene on mig-17. Analysis using the mNeonGreen-FBL-1 reporter revealed that its localization to the gonadal basement membrane was significantly reduced in mig-17, whereas it was recovered to the wild-type levels in mig-17; rpl-20 double mutants. These results indicate that the rpl-20 mutation suppresses mig-17 gonadal defects through dual mechanisms: deceleration of growth rate and enhancement of FBL-1C recruitment to the gonadal basement membrane.

developmental biology↗

bioRxiv2023

Emergence of rhythmic chunking in complex stepping of mice

Motor chunking is important for motor execution, allowing atomization and efficiency of movement sequences. However, it remains unclear why and how chunks contribute to motor execution. To analyze the structure of naturally occurring chunks, we trained mice to run in a complex series of steps and identified the formation of chunks. We found that intervals (cycle) and the positional relationship between the left and right limbs (phase) of steps inside the chunks, unlike those outside the chunks, were consistent across occurrences. Further, licking by the mice was also more periodic and linked to the specific phases of limb movements within the chunk. Based on these findings, we propose the rhythm chunking hypothesis, whereby within chunks, the repetitive movements of many body parts are linked by the rhythm parameters: cycle and phase. The computational complexity of movement may thereby be reduced by adjusting movements as the combination of rhythms.

animal behavior and cognition↗

bioRxiv2022

Germline-specific role for unconventional components of the γ-tubulin complex in Caenorhabditis elegans

The {gamma}-tubulin complex ({gamma}TuC) is a widely conserved microtubule nucleator, but some of its components GCP4-6. Here, we identified two {gamma}TuC-associated proteins in C. elegans, namely GTAP-1 and -2, for which apparent orthologs were detected only in the genus Caenorhabditis. Their centrosomal localization was interdependent. In early C. elegans embryos, whereas the conserved {gamma}TuC component MZT-1/MOZART1 was essential for the localization of centrosomal {gamma}-tubulin, depletion of GTAP-1 and/or -2 caused up to 50% reduction of centrosomal {gamma}-tubulin and precocious disassembly of spindle poles during mitotic telophase. In the adult germline, GTAP-1 and GTP-2 contributed to the efficient recruitment of {gamma}TuC to the plasma membrane. Depletion of GTAP-1, but not GTAP-2, severely disrupted both the microtubule array and the honeycomb-like structure in the adult germline. We propose that GTAP-1 and -2 are unconventional components of {gamma}TuC that contribute to the organization of both centrosomal and non-centrosomal microtubules by targeting the {gamma}TuC to specific subcellular sites in a tissue-specific manner. SUMMARY STATEMENTHaruta et al. show that GTAP-1 and -2, two unconventional components of the {gamma}-tubulin complex ({gamma}TuC) in C. elegans, contribute to targeting the {gamma}TuC to embryonic centrosomes and germ-cell membrane in adults.

cell biology↗