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Biology subjects

King, F.

Publications and source records attributed to King, F..

2 recordsLinked to original sources

LNA043 and ANGPTL3 Interactions with Integrin α5β1 and Fibronectin Drive Distinct Stromal and Immune Responses

Osteoarthritis (OA) is characterized by cartilage breakdown, extracellular matrix remodeling, and synovial inflammation. Dysregulated integrin 5{beta}1 signaling and fibronectin fragmentation are key drivers of OA progression. We found that in ihMSC, LNA043, Full length ANGPTL3 (FL-ANGPTL3, and C-terminal fibronogen-tlike domain of ANGPTL3 (C-ANGPTL3) interacted with both integrin 5{beta}1 and fibronectin, consistent with a multivalent binding mode supported by AlphaFold based structural predictions. FL-ANGPTL3 supported ihMSC adhesion and induced human monocyte migration, with both effects being dependent on integrin {beta}1. C-ANGPTL3 alone was sufficient to mediate these effects, although with reduced efficacy compared to the full-length protein. In contrast, LNA043 did not support ihMSC adhesion but retained integrin {beta}1-dependent monocyte migratory activity, defining a more selective functional profile and indicating that further truncation modulates downstream responses without abolishing integrin engagement. To further explore the biology of ANGPTL3 and the mechanism of action of LNA043 we employed a targeted RASL Seq profiling. We found that both FL- and C-ANGPTL3, but not LNA043, induced broad transcriptional reprogramming and counter regulated fibronectin fragment-driven inflammatory signaling in monocytes. We uncovered a role for ANGPTL3 in fibronectin-integrin 5{beta}1 signaling and showed that LNA043 preserves this interaction while uncoupling it from strong immune responses.

cell biology↗

A broad-host-range Rhizobium rhizogenes strain enables transient expression across diverse crops and establishes functional assays in faba bean

Agrobacterium-mediated transient expression has revolutionized plant research, enabling numerous landmark discoveries across diverse areas of plant biology. Yet this powerful approach remains largely confined to solanaceous species, leaving most economically important crop families without a comparable rapid assay platform. Here, we show that an engineered Rhizobium rhizogenes strain, AS109, mediates efficient transient expression across diverse dicot species spanning multiple taxonomic families, consistently outperforming commonly used laboratory agrobacterial strains. Leveraging the broad host range of AS109, we establish a suite of functional assays in faba bean (Vicia faba), including protein localisation, RNA interference-mediated gene silencing, cell-surface elicitor recognition screens, nucleotide-binding leucine-rich repeat receptor (NLR) activation, and infection cell biology at the host-pathogen interface. We further demonstrate that both singleton NLRs and sensor-helper NLR pairs from Solanaceae retain effector recognition and cell death activity when transferred into faba bean, establishing a rapid platform for evaluating cross-family transferability of disease-resistance genes. AS109 thus provides an accessible and versatile chassis for functional genomics in non-model crops, bridging the widening gap between hypothesis generation and experimental validation across diverse plant species.

plant biology↗