Biology subjects

Varghese, J.

Publications and source records attributed to Varghese, J..

16 recordsLinked to original sources

bioRxiv2026

The innate cytokine IL-18 inhibits CNS autoimmunity through preferential activation of protective CD8 T-cells

Chronic innate immune activation is widely thought to challenge self-tolerance. IL-18 is an inflammasome-activated cytokine and potent amplifier of T-cell activation whose excess is associated with certain autoinflammatory, but not autoimmune, diseases. We tested how excess IL-18 affected susceptibility to experimental autoimmune encephalomyelitis (EAE), a model of CNS autoimmunity driven by IL-18 responsive, myelin-autoreactive CD4 T-cells (CD4Tauto). We hypothesized that IL-18 would exacerbate immunopathology in EAE. Instead, excess IL-18 was profoundly protective. IL-18 did not impair CD4Tauto priming or early expansion. Rather, it selectively restricted later accumulation of highly activated, splenic CD4Tauto bearing CNS-homing integrins. Despite high IL-18 receptor expression on CD4Tauto and Foxp3+ CD4Treg, excess IL-18 acted specifically through mature CD8 T-cells to promote a highly activated CD8Teffector phenotype and IFN{gamma}-dependent protection from EAE. Therapeutic administration of a "decoy-resistant" IL-18 agonist (DR-18) to wild-type mice, even after CD4Tauto expansion, nevertheless engaged CD8 T-cells to diminish CD4Tauto abundance, prevent CNS infiltration, and block immunopathology. Together, these findings demonstrate IL-18s unexpected, dominant ability to mobilize protective CD8 T-cells against highly activated CD4Tauto and protect from CNS autoimmune pathology; illustrating a potential therapeutically relevant mechanism by which autoinflammation actively opposes autoimmunity.

immunology↗

bioRxiv2025

CD36 is a metabolic checkpoint for Th2 cell tissue residency during allergic airway inflammation

The prevalence of allergic diseases, including asthma, continues to rise in industrialized societies, yet the mechanisms sustaining pathogenic T helper 2 (Th2) responses remain incompletely understood. Here, we show that patients with allergic asthma exhibit elevated lipophilic volatile organic compounds in exhaled air and altered fatty acid-metabolism gene expression in sputum-derived Th2 cells. Using a mouse model of house dust mite-induced allergic airway inflammation, we find that the lipid transporter CD36 is dispensable for T follicular helper and germinal center B cell responses but is critical for maintaining lung-resident memory Th2 cells. CD36 regulates GATA3 and PPAR{gamma} expression in lung-resident memory Th2 cells and their interaction with type-2 conventional dendritic cells during airway inflammation. In human T cells, pharmacological inhibition of CD36 does not impair initial activation but blocks terminal Th2 differentiation. These findings identify CD36 as a metabolic checkpoint that sustains Th2 effector function and tissue residency, and establish lipid metabolism as a yet unrecognized therapeutic target in allergic asthma. SummaryAllergic asthma is marked by rising prevalence yet the drivers of persistent T helper 2 (Th2) immunity remain unclear. We show that asthma patients exhibit altered fatty acid-metabolism signatures in sputum Th2 cells and elevated lipophilic volatile organic compounds in exhaled air. In a mouse model of house dust mite-induced airway inflammation, the lipid transporter CD36 was dispensable for germinal center responses but essential for lung-resident memory Th2 cells, controlling GATA3 and PPAR{gamma} expression and promoting cDC2 interactions. Pharmacological inhibition of CD36 in human T cells preserved activation but blocked terminal Th2 differentiation. These findings identify CD36 as a metabolic checkpoint that sustains Th2 effector function and tissue residency, and nominate it as a therapeutic target in allergic asthma. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/676489v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@117da6eorg.highwire.dtl.DTLVardef@105934corg.highwire.dtl.DTLVardef@109903corg.highwire.dtl.DTLVardef@dc9345_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Longitudinal TCR repertoires in ulcerative colitis patients show features distinguishing disease states

ABSTRACT AND KEY WORDSO_ST_ABSBackgroundC_ST_ABSUlcerative colitis (UC) affects an estimated 10 million people worldwide. The exact etiology of the disease is unknown, but T cell dysregulation and aberrant activation is associated with UC--prompting research into T cell receptor (TCR) repertoires in UC patients. However, few studies have compared UC patients TCR repertoires in flare (inflamed) and remission (uninflamed) states. Moreover, this is the first dataset to our knowledge examining multiple repertoires from UC patients over time, enabling longitudinal analyses. MethodsTCR repertoires were obtained for 21 patients across multiple timepoints, yielding a total of 58 samples. Repertoires clonality, diversity, overlap, and gene usage frequencies were compared across all patients. CDR3 sequences were split into K-mers (sequences of length K), and enriched K-mers in flare and remission states were identified using GLIPH2. ResultsAlthough repertoires vary across patients, there were significant differences in the usage of 20 V{beta} genes across flare and remission states. Moreover, calculating the overlap in repertoires with enriched K-mers showed higher overlap scores than when using full TCR sequences. 622 unique enriched K-mers were identified in flare states and 495 in remission states, with only 57 overlapping between the two states. ConclusionsOverall, these results highlight the importance of analyzing V{beta} gene usage and K-mer enrichment in TCR repertoires, particularly given the lack of public clones across patient cohorts. Future studies characterizing the specific antigenic targets associated with these features will pave the way for biomarker discovery in UC. KEY MESSAGESO_LIWhat is already known? UC is a chronic condition characterized by fluctuating periods of flares and remissions, as well as aberrant immune activity. C_LIO_LIWhat is new here? TCR repertoires were obtained from UC patients colonoscopies, with multiple timepoints per patient--enabling the analysis of repertoire characteristics within and across patients over time. C_LIO_LIHow can this study help patient care? Understanding the exact immune mechanisms in UC can pave the way for biomarker discovery and advance the state of care for patients, given that current treatments are non-specific and have adverse side effects. C_LI SummaryThis article presents an analysis of T cell receptor repertoires from ulcerative colitis patient samples collected during colonoscopies, identifying genes and motifs associated with patients flare (inflamed) and remission (uninflamed) states.

immunology↗

bioRxiv2025

NAMPT activity plays a key role in driving autoimmune processes that characterize type 1 diabetes development in mice

Type 1 diabetes (T1D) is characterised by destruction of pancreatic beta cells by islet-infiltrating cytotoxic lymphocytes, and elevated intra-islet secretion of pro-inflammatory cytokines. However, the underlying pathophysiological mechanisms remain incompletely understood. We hypothesised that abnormal elevation of islet NAD, via activation of NAMPT, plays a key role in driving islet autoimmune processes in T1D. Here, we report that NAMPT inhibition protects against pro-inflammatory cytokine (IL-1{beta}, TNF and IFN{gamma}) mediated beta-cell dysfunction and apoptosis in isolated mouse and human islets. RNAseq revealed that NAMPT inhibition blocked cytokine-mediated gene expression linked to pro-inflammatory responses and leukocyte migration. In vivo, diabetes was induced in CD1 mice via multiple low dose streptozotocin (MLDS) injection. MLDS mice were administered the NAMPT inhibitor FK866 (10 mg/kg; IP) or saline equivalent for 16 days. These experiments demonstrated that NAMPT inhibition improved glycaemic control and beta-cell function and insulin content in MLDS mice. FK866 also reduced proportions of islet-residing TNF-producing CD4+T-cells and F4/80+macrophages, proliferation of spleen-derived CD4+ and CD8+T-cells, and proliferation of islet-derived CD4+T-cells and F4/80+macrophages. Finally, we report that NAMPT inhibition was able to block pro-inflammatory cytokine-mediated migration of cytotoxic CD8+T-cells into isolated islets, using an in vitro transwell platform. This data supports a key immunomodulatory role for NAMPT in islet autoimmunity. NAMPT inhibition may represent a novel therapeutic approach for T1D. The effects of increased NAD levels on islet inflammation require in-depth characterisation, and caution should be exercised with regard to use of NAD boosting supplements, particularly in individuals at risk of developing T1D.

cell biology↗

bioRxiv2024

miR-184 controls Dilp8 to regulate the timing of a critical developmental transition in Drosophila melanogaster

Organismal development depends on the precise coordination of growth and developmental timing, which is regulated by a complex interplay of intrinsic and extrinsic factors. However, the mechanisms underlying this regulation are not fully understood. Post-transcriptional regulation by microRNAs (miRNAs) plays a pivotal role in ensuring the proper timing of gene expression necessary for growth and development. In this study, we conducted a genetic screen to identify microRNAs that regulate developmental timing in Drosophila. Our screen identified miR-184, previously implicated in germline maturation and embryonic development, as a regulator of pupariation timing by acting in the larval imaginal discs. Using genetic and molecular approaches, we identified Drosophila insulin-like peptide 8 (Dilp8), a paracrine factor critical for regulating developmental stability, as a target of miR-184. During normal larval development miR-184 facilitates timely pupariation by regulating dilp8 levels. Furthermore, we demonstrate that miR-184 plays a critical role in tissue damage responses by inducing dilp8 expression, which delays pupariation to enable damage repair mechanisms. These findings reveal a novel post-transcriptional regulatory mechanism that links miR-184 to the control of developmental timing under normal growth conditions and in response to tissue damage.

developmental biology↗

bioRxiv2024

Microvascular immunity is organ-specific and concealed in peripheral blood

Blood tests are a common method for diagnosing and monitoring various health conditions. Nevertheless, the extent to which phlebotomy can offer insights into immune and organ dysfunction remains uncertain. Here, we conducted a comprehensive analysis of blood-borne leukocytes in the microvasculature of different mouse organs and compared it to peripheral blood and parenchymal samples. We observed that microvascular immune cells outnumber tissue-resident counterparts in the kidney, liver and lung. Classical monocytes and lymphocytes are diminished while nonclassical and SSC-high monocytes are enriched compared to blood. Utilizing single-cell sequencing, we identified specific cell populations up to 100-fold expanded in the kidney vasculature including macrophages, plasmacytoid dendritic cells, B cells, and innate lymphoid cells type 2. Microvascular enrichment could trigger a local phenotype switch as shown in glomerulus-restricted B cells. Peritonitis and acute kidney injury (AKI) elicited a multifaceted and systemic response of microvascular leukocytes. It involved remote organ effects, such as a 16-fold increase of leukocytes in the splenic circulation or 64-fold increase of SSC-high monocytes in the liver circulation that was not detectable in the peripheral blood or the tissue. Following full recovery from AKI, persistent and complex changes were observed predominantly in the renal vasculature, while most leukocytes in the peripheral blood had already returned to baseline levels. Collectively, our findings suggest a paradigm of organ- and disease-specific microvascular immunity that largely eludes conventional blood and tissue analysis.

immunology↗

bioRxiv2024

PuMA: PubMed Gene-Celltype-Relation Atlas

Rapid extraction and visualization of cell-specific gene expression is important for automatic celltype annotation, e.g. in single cell analysis. There is an emerging field in which tools such as curated databases or Machine Learning methods are used to support celltype annotation. However, complementing approaches to efficiently incorporate latest knowledge of free-text articles from literature databases, such as PubMed are understudied. This work introduces the PubMed Gene/Celltype-Relation Atlas (PuMA) which provides a local, easy-to-use web-interface to facilitate automatic celltype annotation. It utilizes pretrained large language models in order to extract gene and celltype concepts from Pub-Med and links biomedical ontologies to suggest gene to celltype relations. It includes a search tool for genes and cells, additionally providing an interactive graph visualization for exploring cross-relations. Each result is fully traceable by linking the relevant PubMed articles. The software framework is freely available and enables regular article imports for incremental knowledge updates. GitLab: imigitlab.uni-muenster.de/published/PuMA

bioinformatics↗

bioRxiv2023

Genome-wide DNA methylation changes in human spermatogenesis

Sperm production and function require the correct establishment of DNA methylation patterns in the germline. Here, we examined the genome-wide DNA methylation changes during human spermatogenesis and its alterations in disturbed spermatogenesis. We found that spermatogenesis is associated with remodeling of the methylome, comprising a global-decline in DNA methylation in primary spermatocytes followed by selective remethylation, resulting in a spermatid-specific methylome. Hypomethylated regions in spermatids were enriched in specific transcription factor binding sites for DMRT and SOX family members and spermatid-specific genes. Intriguingly, while SINEs displayed differential methylation throughout spermatogenesis, LINEs appeared to be protected from changes in DNA methylation. In disturbed spermatogenesis, germ cells exhibited considerable DNA methylation changes, which were significantly enriched at transposable elements and genes involved in spermatogenesis. We detected hypomethylation in SVA and L1HS in disturbed spermatogenesis, suggesting an association between the abnormal programming of these regions and failure of germ cells progressing beyond meiosis.

genetics↗

bioRxiv2023

Data-driven signal analysis of sensory cortical processing using high-resolution fMRI across different studies

The analysis of large data sets within and across preclinical studies has always posed a particular challenge in terms of data volume and method heterogeneity between studies. Recent developments in machine learning (ML) and artificial intelligence (AI) allow to address these challenges in complex macro- and microscopic data sets. Because of their complex data structure, functional magnetic resonance imaging (fMRI) measurements are perfectly suited to develop such ML/AI frameworks for data-driven analyses. These approaches have the potential to reveal patterns, including temporal kinetics, in blood-oxygen-level-dependent (BOLD) time series with a reduced workload. However, the typically poor signal-to-noise ratio (SNR) and low temporal resolution of fMRI time series have so far hampered such advances. Therefore, we used line scanning fMRI measurements with high SNR and high spatio-temporal resolution obtained from three independent studies and two imaging centers with heterogeneous study protocols. Unbiased time series clustering techniques were applied for the analysis of somatosensory information processing during electrical paw and optogenetic stimulation. Depending on the similarity formulation, our workflow revealed multiple patterns in BOLD time series. It produced consistent outcomes across different studies and study protocols, demonstrating the generalizability of the data-driven method for cross-study analyzes. Further, we introduce a statistical analysis that is entirely based on cluster distribution. Using this method, we can reproduce previous findings including differences in temporal BOLD characteristics between two stimulation modalities. Our data-driven approach proves high sensitivity, robustness, reproducibility, and generalizability and further quickly provides highly detailed insight into characteristics of BOLD time series. Therefore, it holds great potential for further applications in fMRI data including whole-brain task and resting-state fMRI, which can support fMRI routines. Furthermore, the analytic framework can be used for datasets that have a time-dependent data structure to integrate study results and create robust and generalizable datasets, despite different study protocols.

neuroscience↗

bioRxiv2023

Regulation of Human PINK1 ubiquitin kinase by Serine167, Serine228 and Cysteine412 phosphorylation

Loss-of-function mutations in the human PINK1 kinase (hPINK1) are causative of early-onset Parkinsons disease (PD). Activation of hPINK1 induces phosphorylated ubiquitin to initiate removal of damaged mitochondria by autophagy. Previously we solved the structure of the insect PINK1 orthologue, Tribolium castaneum PINK1, and showed that autophosphorylation of Ser205 was critical for ubiquitin interaction and phosphorylation (Kumar, Tamjar, Waddell et al., 2017). In this advance, we report new findings on the regulation of hPINK1 by phosphorylation. We reconstitute E. coli expressed hPINK1 activity in vitro by direct incorporation of phosphoserine at the equivalent site Serine 228 (pSer228), providing direct evidence for a role for Ser228 phosphorylation in hPINK1 activation. Furthermore, using mass spectrometry, we identify six novel Ser/Thr autophosphorylation sites including regulatory Serine167 phosphorylation (pSer167), which in addition to pSer228 is required for ubiquitin recognition and phosphorylation. Strikingly, we also detect phosphorylation of a conserved Cysteine412 (pCys412) residue in the hPINK1 activation segment. Structural modelling suggests that pCys412 inhibits ubiquitin recognition and we demonstrate that mutation of Cys412 to Ala renders hPINK1 more active towards ubiquitin when expressed in human cells. These results outline new insights into hPINK1 activation by pSer167 and pSer228 and a novel inhibitory mechanism mediated by pCys412. These findings will aid in the development of small molecule activators of hPINK1.

biochemistry↗

bioRxiv2021

Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin

Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations are unclear. In order to assess this, we studied how IR and associated inflammation in adipose tissue developed in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1-/-) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in tissue, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1-/- mice gained less body weight and developed less IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype. These observations suggest a novel role of hepcidin (central regulator of systemic iron homeostasis) in the development of inflammation in adipose tissue and insulin resistance, in response to a high-fat diet. CLINICAL PERSPECTIVESO_LIElevated body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying molecular mechanisms linking them are unclear. C_LIO_LIIn response to high-fat diet (HFD)-feeding (to induce IR), mice that lacked hepcidin (Hamp1-/-) (and hence had elevated body iron stores) gained less body weight and developed less insulin resistance than wild-type (WT) mice. Inflammation and infiltration of macrophages into adipose tissue of HFD-fed Hamp1-/- mice were less than in WT mice, with the macrophages exhibiting an anti-inflammatory M2-like phenotype. C_LIO_LIThese findings suggest a novel role of iron and hepcidin in HFD-induced inflammation in adipose tissue and development of insulin resistance. They raise the possibility that modulation of body iron may represent a potential way to inhibit these processes. C_LI

immunology↗

bioRxiv2020

Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection

BackgroundSARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation of severe disease, and characterization of long-term immunity. Initial observations suggest that severe disease is associated with higher antibody levels and greater B cell/plasmablast responses. A multi-antigen immunoassay to define the complex serological landscape and clinical associations is essential. MethodsWe developed a multiplex immunoassay and evaluated serum/plasma from adults with RT-PCR-confirmed SARS-CoV-2 infections during acute illness (N=52) and convalescence (N=69); and pre-pandemic (N=106) and post-pandemic (N=137) healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 Nucleocapsid (N), Spike domain 1 (S1), receptor binding domain (S1-RBD) and S1-N-terminal domain (S1-NTD). ResultsTo diagnose infection, the combined [IgA+IgG+IgM] or IgG for N, S1, and S1-RBD yielded AUC values -0.90 by ROC curves. From days 6-30 post-symptom onset, the levels of antigen-specific IgG, IgA or [IgA+IgG+IgM] were higher in patients with severe/critical compared to mild/moderate infections. Consistent with excessive concentrations of antibodies, a strong prozone effect was observed in sera from severe/critical patients. Notably, mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared to severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 months. ConclusionThis SARS-CoV-2 multiplex immunoassay measures the magnitude, complexity and kinetics of the antibody response against multiple viral antigens. The IgG and combined-isotype SARS-CoV-2 multiplex assay is highly diagnostic of acute and convalescent disease and may prognosticate severity early in illness. One Sentence SummaryIn contrast to patients with moderate infections, those with severe COVID-19 develop prominent, early antibody responses to S1 and N proteins.

immunology↗

bioRxiv2019

Edem1 activity in the fat body regulates insulin signalling and metabolic homeostasis in Drosophila

In Drosophila, nutrient status is sensed by the fat body, a functional homolog of mammalian liver and white adipocytes. The fat body conveys nutrient information to insulin-producing cells (IPCs) through humoral factors which regulate Drosophila insulin-like peptide (DILP) levels and insulin signalling. Insulin signalling has pleiotropic functions, which include the management of growth and metabolic pathways. Here, we report that Edem1 (endoplasmic reticulum degradation-enhancing -mannosidase-like protein 1), an endoplasmic reticulum-resident protein involved in protein quality control, acts in the fat body to regulate insulin signalling and thereby the metabolic status in Drosophila. Edem1 limits the fat body derived Drosophila TNF Eiger activity on IPCs and maintains systemic insulin signalling in fed conditions. During food deprivation, edem1 gene expression levels drop, which aids in the reduction of systemic insulin signalling crucial for survival. Overall we demonstrate that Edem1 plays a vital role in helping the organism to endure a fluctuating nutrient environment by managing insulin signalling and metabolic homeostasis.

developmental biology↗

bioRxiv2018

FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning

The concerted action of many protein kinases helps orchestrate the error-free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin-dependent kinases, are well-established. However, these and other known mitotic kinases alone cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis. Here we demonstrate that CK1, of the casein kinase 1 family of protein kinases, localises to the spindle and is required for proper spindle-positioning and timely cell division. CK1 is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1-binding-deficient FAM83DF283A/F283A knockin mutation, display pronounced spindle-positioning defects, and a prolonged mitosis. Restoring FAM83D at the endogenous locus in FAM83D-/- cells, or artificially delivering CK1 to the spindle in FAM83DF283A/F283A cells, rescues these defects. These findings implicate CK1 as new mitotic kinase that orchestrates the kinetics and orientation of cell division.

cell biology↗

bioRxiv2018

Insulin signalling activates multiple feedback loops to elicit hunger-induced feeding in Drosophila

Insulin, a highly conserved peptide hormone, links nutrient availability to metabolism and growth in animals. Besides this, in fed states insulin levels are high and insulin acts as a satiety hormone. In animals that are food deprived insulin levels remain low which facilitates hunger induced feeding. Contrary to expectations, we present evidence for persistent Drosophila insulin-like peptide gene expression and insulin signalling during initial phases of starvation. Maintenance of insulin signalling is crucial to sustain feeding responses during initial stages of starvation. Insulin signalling acts in a feedback loop involving the abdominal fatbody to maintain dilp gene expression in the early stages of food deprivation. Furthermore, another feedback regulatory loop between insulin-producing cells (IPCs) and neurons that produce the orectic hormone short-neuropeptide-F (sNPF), maintains sNPF levels and triggers feeding behavior. Thus, insulin acts through multiple feedback regulatory loops to elicit orexigenic responses and aid in efficient utilization of energy stores during early starvation.

developmental biology↗

bioRxiv2017

FAM83G/PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

Our previous studies of PAWS1 (Protein Associated With SMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration.\n\nSummary statementPAWS1/FAM83G controls cell migration by influencing the organisation of F-actin and focal adhesions and the distribution of the actin stress fibre network through its association with CD2AP.

cell biology↗