Biology subjects

Dutta, P.

Publications and source records attributed to Dutta, P..

42 records · Page 3Linked to original sources

bioRxiv2019

Planar cell polarity in the C. elegans embryo emerges by differential retention of aPARs at cell-cell contacts

Formation of the anteroposterior and dorsoventral body axis in the Caenorhabditis elegans embryo depends on cortical actomyosin flows and advection of polarity determinants. The role of this patterning mechanism in tissue polarization immediately after formation of cell-cell contacts is not fully understood. Here, we demonstrate that planar cell polarity (PCP) is established in the C. elegans embryo at the time of left-right (l/r) symmetry breaking. At this stage, centripetal cortical flows asymmetrically and differentially advect anterior polarity determinants (aPARs) PAR-3, PAR-6 and PKC-3 from cell-cell contacts to the medial cortex, which results in their unmixing from apical myosin. Advection generally requires GSK-3 and CDC-42, while advection of PAR-6 specifically depends on the RhoGAP PAC-1. Concurrent asymmetric retention of PAR-3, E-cadherin/HMR-1, PAC-1 and opposing retention of the antagonistic Wnt pathway components APC/APR-1 and Frizzled/MOM-5 at apical cell-cell contacts leads to planar asymmetries. The most obvious mark of PCP, asymmetric retention of PAR-3 at posterior cell-cell contacts on the left side of the embryo, is required for proper cytokinetic cell intercalation. Hence, our data uncover how PCP can be established through Wnt signaling as well as dissociation and planar asymmetric retention of aPARs mediated by distinct Rho GTPases and their regulators.

cell biology↗

bioRxiv2019

Genomic analyses underpin the feasibility of concomitant genetic improvement of milk yield and mastitis resistance in dairy sheep

Milk yield is the most important dairy sheep trait and constitutes the key genetic improvement goal via selective breeding. Mastitis is one of the most prevalent diseases, significantly impacting on animal welfare, milk yield and quality, while incurring substantial costs. Our objectives were to determine the feasibility of a concomitant genetic improvement programme for enhanced milk production and resistance to mastitis. Individual records for milk yield and four mastitis-related traits were collected monthly throughout lactation for 609 ewes of the Chios breed. All ewes were genotyped with a mastitis specific custom-made 960 single nucleotide polymorphism array. We performed genomic association studies, (co)variance component estimation and pathway enrichment analysis, and characterised gene expression levels and the extent of allelic expression imbalance. Presence of heritable variation for milk yield was confirmed. There was no significant genetic correlation between milk yield and mastitis. Environmental factors appeared to favour both milk production and udder health. Four Quantitative Trait Loci (QTLs) affecting milk yield were detected on chromosomes 2, 12, 16 and 19, in locations distinct from those previously identified to affect mastitis resistance. Pathways, networks and functional gene clusters for milk yield were identified. Seven genes (DNAJA1, DNAJC10, FGF10, GHR, HMGCS1, LYPLA1, OXCT1) located within the QTL regions were highly expressed in both the mammary gland and milk transcriptome, suggesting involvement in milk synthesis and production. Furthermore, the expression of four genes (DNAJC10, FGF10, OXCT1, EMB) was enriched in immune tissues implying a favourable pleiotropic effect or likely role in milk production during udder infection. In conclusion, the absence of genetic antagonism between milk yield and mastitis resistance suggests that simultaneous genetic improvement of both traits be achievable. The detection of milk yield QTLs with the mastitis array underpins the latters utility as a breeding tool for the genetic enhancement of both traits.

genetics↗

bioRxiv2018

nPIST: A Novel Actin Binding Protein of trans-Golgi Network

npist is the neuronal isoform of PIST, a trans-golgi associated protein involved in major modulation of vesicular trafficking. nPIST interacts with glutamate delta2 receptor (GluR{delta}2) in Purkinje cells. Our study shows nPIST as a novel actin binding protein. Our structure based sequence analysis shows nPIST contains one WH2-like domain. Further our experimental analysis illustrates that fragment of nPIST consisting of WH2-like domain binds to actin. Moreover it was found that nPIST contains several regions involved in interaction with actin. The binding of nPIST to actin through multiple actin binding regions facilitated actin filament stabilization in vitro. In vivo, nPIST localized actin in perinuclear region as a blotch when ectopically expressed.

cell biology↗

bioRxiv2017

Presence of WH2 like domain in VgrG-1 toxin of Vibrio cholerae reveals the molecular mechanism of actin cross-linking

Type VI secretion systems (T6SS) plays a crucial role in Vibrio cholerae mediated pathogenicity and predation. Tip of T6SS is homologous to gp27/gp5 complex or tail spike of T4 bacteriophage. VgrG-1 of V. cholerae T6SS is unusual among other VgrG because its effector domain is trans-located into the cytosol of eukaryotic cells with an additional actin cross-linking domain (ACD) at its C terminal end. ACD of VgrG-1 (VgrG-1-ACD) causes T6SS dependent host cell cytotoxicity through actin cytoskeleton disruption to prevent bacterial engulfment by macrophages. ACD mediated actin cross-linking promotes survival of the bacteria in the small intestine of humans, along with other virulence factors; establishes successful infection with the onset of diarrhoea in humans. Our studies demonstrated VgrG-1-ACD can bind to actin besides actin cross-linking activity. Computational analysis of ACD revealed the presence of WH2 domain through which it binds actin. Mutations in WH2 domain lead to loss of actin binding in vitro. VgrG-1-ACD having the mutated WH2 domain cannot cross-link actin efficiently in vitro and manifests less actin cytoskeleton disruption when transfected in HeLa cells.\n\nSummary statementActin cross-linking (ACD) domain of VgrG-1 toxin of Type VI secretion in Vibrio cholera has WASP Homology domain 2 (WH2) domain. ACD interact with actin through WH2 domain, WH2 is essential for ACD mediated cross-linking and disruption of actin cytoskeleton in the host cell.

biochemistry↗

bioRxiv2017

A Negative Feedback Regulates The Flow Of Signal Through Akt/mTORC1/S6K1 Pathway

AbstractSeveral growth factors, cytokines, hormones activate PI3K/Akt pathway. Akt is a key node in this pathway and activates different downstream paths. One such path is Akt/mTORC1/S6K1 that controls protein synthesis, cell survival, and proliferation. Here we show that a negative feedback controls activation of S6K1 through this pathway. Due to this negative feedback, a sustained phospho-Akt signal generates a transient pulse of phospho-S6K1. We have created a mathematical model for this circuit. Analysis of this model shows that the negative feedback acts as a filter and preferentially allows a signal, with sharp and faster rise of phospho-Akt, to induce pronounced activation of S6K1. It blocks an input with a fast oscillation of phospho-Akt to flow through this path. We show that this negative feedback leads to differential activation of S6K1 by Insulin and Insulin-like Growth Factor 1. Such differential effect may explain the difference in the mitogenic effect of these two molecules.

systems biology↗

bioRxiv2016

Non Diaphanous Formin Delphilin Acts as a Barbed End Capping Protein

Formins are important for actin polymerization. Delphilin is a unique formin having PDZ domains and FH1, FH2 domains at its N and C terminus respectively. In this study we observed that Delphilin binds to actin filaments, and have negligible actin filament polymerizing activity. Delphilin inhibits actin filament elongation like barbed end capping protein CapZ. In vitro, Delphilin stabilized actin filaments by inhibiting actin filament depolymerisation. Therefore, our study demonstrates Delphilin as an actin-filament capping protein.

cell biology↗